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Issue 8,2026 Table of Contents
2026, 33(8):811-821.
DOI: 10.3872/j.issn.1007-385X.2026.08.001
Abstract:
Circulating tumor cells (CTCs), regarded as the “seed cells” of tumor metastasis, are closely associated with tumor progression, therapeutic response, and patient prognosis through changes in their abundance, molecular phenotypes, and functional states. With the development of precision oncology, CTC detection has gradually evolved from simple enumeration toward molecular subtyping and therapeutic decision support. In recent years, nanopeptide-based CTC enrichment and subtyping platforms have emerged as promising liquid biopsy technologies. By integrating peptide-functionalized magnetic nanobead-mediated enrichment with multidimensional molecular profiling, these platforms can improve the capture of rare CTCs and provide a cellular basis for therapeutic target detection, treatment monitoring, and early warning of drug resistance. The nanopeptide-based CTC detection technology developed by the National Center for Nanoscience and Technology, China (NCNST) has established a clinically accessible detection system with high sensitivity and specificity, promoting the transition of CTC detection from “quantitative assessment” to a 2.0 era centered on molecular subtyping and treatment decision support. This review focuses on the core principles, key technological breakthroughs, and clinical translational value of nanopeptide-based CTC detection platforms in precision cancer biotherapy, and discusses the challenges related to standardization, cost control, level of clinical evidence, and translation into companion diagnostics, to provide a reference for optimizing precision biotherapeutic strategies in oncology.
Circulating tumor cells (CTCs), regarded as the “seed cells” of tumor metastasis, are closely associated with tumor progression, therapeutic response, and patient prognosis through changes in their abundance, molecular phenotypes, and functional states. With the development of precision oncology, CTC detection has gradually evolved from simple enumeration toward molecular subtyping and therapeutic decision support. In recent years, nanopeptide-based CTC enrichment and subtyping platforms have emerged as promising liquid biopsy technologies. By integrating peptide-functionalized magnetic nanobead-mediated enrichment with multidimensional molecular profiling, these platforms can improve the capture of rare CTCs and provide a cellular basis for therapeutic target detection, treatment monitoring, and early warning of drug resistance. The nanopeptide-based CTC detection technology developed by the National Center for Nanoscience and Technology, China (NCNST) has established a clinically accessible detection system with high sensitivity and specificity, promoting the transition of CTC detection from “quantitative assessment” to a 2.0 era centered on molecular subtyping and treatment decision support. This review focuses on the core principles, key technological breakthroughs, and clinical translational value of nanopeptide-based CTC detection platforms in precision cancer biotherapy, and discusses the challenges related to standardization, cost control, level of clinical evidence, and translation into companion diagnostics, to provide a reference for optimizing precision biotherapeutic strategies in oncology.
Zhou Yanxing
,
Zuo Changjun
,
Zheng Rui
,
Chen Lei
,
Jie Yongsheng
,
Shu Xiong
,
Zhou Yanfang
,
Zhan Yi
2026, 33(8):822-829.
DOI: 10.3872/j.issn.1007-385X.2026.08.002
Abstract:
Objective: To investigate the effects of the HSP90β-targeting monoclonal antibody 2G1 on the biological characteristics of MG-63 sphere cells, an osteosarcoma stem cell (OSC)-enriched model, and to explore its association with changes in Wnt signaling-related proteins. Methods: MG-63 sphere cells were generated from the human osteosarcoma cell line MG-63 by serum-free suspension culture. The target antigen recognized by monoclonal antibody 2G1 was identified by immunofluorescence co-localization and co-immunoprecipitation assays. Flow cytometry was used to determine the expression of cell surface HSP90β in parental MG-63 cells and MG-63 sphere cells. Methylcellulose sphere formation, Transwell migration, and invasion assays were performed to evaluate the effects of 2G1 on the sphere-forming, migratory, and invasive capacities of MG-63 sphere cells. A nude mouse subcutaneous xenograft model was established to assess the effect of 2G1 on the tumorigenic potential of MG-63 sphere cells in vivo. Transcriptome sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Western blotting were further performed to investigate alterations in signaling pathways and the expression of proteins associated with stem-like characteristics, epithelial-mesenchymal transition (EMT)-related markers, and the Wnt/β-catenin signaling pathway following 2G1 treatment. Results: Immunofluorescence co-localization and co-immunoprecipitation demonstrated that HSP90β was the target antigen recognized by monoclonal antibody 2G1. Flow cytometric analysis showed that the proportion of HSP90β-positive cells on the cell surface was significantly higher in MG-63 sphere cells than in parental MG-63 cells [(20.77 ± 1.29)% vs (2.87 ± 0.33)%, P < 0.001]. Compared with the control group, 2G1 treatment significantly reduced the number of spheres formed (82.67 ± 4.70 vs 42.67 ± 4.00), migrated cells (117.00 ± 5.57 vs 78.33 ± 5.03), and invaded cells (130.70 ± 5.03 vs 89.33 ± 5.03) (all P < 0.001). In the nude mouse xenograft model, 2G1 treatment suppressed tumor growth, with tumor weight and tumor volume inhibition rates of (31.83 ± 16.36)% and (22.00 ± 15.48)% , respectively. Transcriptome sequencing identified 698 differentially expressed genes, including 329 upregulated and 369 downregulated genes. KEGG enrichment analysis indicated enrichment of differentially expressed genes in the Wnt signaling pathway. Western blotting analysis further demonstrated that the expression levels of SOX2, OCT4, N-cadherin, phosphorylated β-catenin (p-β-catenin), and c-Myc were significantly decreased, whereas E-cadherin expression was significantly increased following 2G1 treatment (all P < 0.001). Conclusion: Cell surface HSP90β is highly expressed in MG-63 sphere cells. Targeting HSP90β with monoclonal antibody 2G1 suppresses the sphere-forming, migratory, invasive, and tumorigenic capacities of MG-63 sphere cells and alters the expression levels of stem cell markers, EMT-related markers, and Wnt/β?catenin signaling pathway proteins. These findings suggest that HSP90β may contribute to the regulation of osteosarcoma stem-like characteristics in MG-63 sphere cells and may represent a potential therapeutic target for osteosarcoma.
Objective: To investigate the effects of the HSP90β-targeting monoclonal antibody 2G1 on the biological characteristics of MG-63 sphere cells, an osteosarcoma stem cell (OSC)-enriched model, and to explore its association with changes in Wnt signaling-related proteins. Methods: MG-63 sphere cells were generated from the human osteosarcoma cell line MG-63 by serum-free suspension culture. The target antigen recognized by monoclonal antibody 2G1 was identified by immunofluorescence co-localization and co-immunoprecipitation assays. Flow cytometry was used to determine the expression of cell surface HSP90β in parental MG-63 cells and MG-63 sphere cells. Methylcellulose sphere formation, Transwell migration, and invasion assays were performed to evaluate the effects of 2G1 on the sphere-forming, migratory, and invasive capacities of MG-63 sphere cells. A nude mouse subcutaneous xenograft model was established to assess the effect of 2G1 on the tumorigenic potential of MG-63 sphere cells in vivo. Transcriptome sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Western blotting were further performed to investigate alterations in signaling pathways and the expression of proteins associated with stem-like characteristics, epithelial-mesenchymal transition (EMT)-related markers, and the Wnt/β-catenin signaling pathway following 2G1 treatment. Results: Immunofluorescence co-localization and co-immunoprecipitation demonstrated that HSP90β was the target antigen recognized by monoclonal antibody 2G1. Flow cytometric analysis showed that the proportion of HSP90β-positive cells on the cell surface was significantly higher in MG-63 sphere cells than in parental MG-63 cells [(20.77 ± 1.29)% vs (2.87 ± 0.33)%, P < 0.001]. Compared with the control group, 2G1 treatment significantly reduced the number of spheres formed (82.67 ± 4.70 vs 42.67 ± 4.00), migrated cells (117.00 ± 5.57 vs 78.33 ± 5.03), and invaded cells (130.70 ± 5.03 vs 89.33 ± 5.03) (all P < 0.001). In the nude mouse xenograft model, 2G1 treatment suppressed tumor growth, with tumor weight and tumor volume inhibition rates of (31.83 ± 16.36)% and (22.00 ± 15.48)% , respectively. Transcriptome sequencing identified 698 differentially expressed genes, including 329 upregulated and 369 downregulated genes. KEGG enrichment analysis indicated enrichment of differentially expressed genes in the Wnt signaling pathway. Western blotting analysis further demonstrated that the expression levels of SOX2, OCT4, N-cadherin, phosphorylated β-catenin (p-β-catenin), and c-Myc were significantly decreased, whereas E-cadherin expression was significantly increased following 2G1 treatment (all P < 0.001). Conclusion: Cell surface HSP90β is highly expressed in MG-63 sphere cells. Targeting HSP90β with monoclonal antibody 2G1 suppresses the sphere-forming, migratory, invasive, and tumorigenic capacities of MG-63 sphere cells and alters the expression levels of stem cell markers, EMT-related markers, and Wnt/β?catenin signaling pathway proteins. These findings suggest that HSP90β may contribute to the regulation of osteosarcoma stem-like characteristics in MG-63 sphere cells and may represent a potential therapeutic target for osteosarcoma.
2026, 33(8):830-839.
DOI: 10.3872/j.issn.1007-385X.2026.08.003
Abstract:
Objective: To investigate the role of RING finger protein 8 (RNF8) in cisplatin (CDDP) sensitivity in endometrial cancer (EC) and its possible mechanism. Methods: The expression level of RNF8 in endometrial cancer tissues and its copy number variation profile were analyzed using an online database. Lentivirus-mediated shRNA was used to stably knock down RNF8 expression in Ishikawa cells, followed by CDDP treatment. The cells were grouped: sh-NC + solvent control, sh-RNF8 + solvent control, sh-NC + CDDP, and sh-RNF8 + CDDP. An inhibition experiment was conducted using the sh-RNF8 + CDDP + KU60019 combination. CCK-8 assays, colony formation assays, Annexin V-FITC/PI flow cytometry, Hoechst 33258/PI staining, WB, and γ-H2AX immunofluorescence were used to assess cell viability, colony formation, apoptosis, DNA damage, and the expression of proteins related to the ATM/CHK2 pathway. Results: RNF8 was significantly overexpressed in endometrial cancer tissues and cells. RNF8 knockdown reduced cell viability and IC50, inhibited colony formation, and further enhanced CDDP-induced apoptosis. Meanwhile, the expression of BAX, Cleaved-Caspase-3, and γ-H2AX increased, while the expression of BCL-2, p-ATM, p-CHK2, and RAD21 decreased. Treatment with KU60019 further promoted DNA damage and apoptosis, and reduced cell viability. Conclusion: RNF8 may promote DNA damage response and reduce the sensitivity of endometrial cancer cells to CDDP via the ATM/CHK2 axis. Knocking down RNF8 increases DNA damage and enhances sensitivity to CDDP.
Objective: To investigate the role of RING finger protein 8 (RNF8) in cisplatin (CDDP) sensitivity in endometrial cancer (EC) and its possible mechanism. Methods: The expression level of RNF8 in endometrial cancer tissues and its copy number variation profile were analyzed using an online database. Lentivirus-mediated shRNA was used to stably knock down RNF8 expression in Ishikawa cells, followed by CDDP treatment. The cells were grouped: sh-NC + solvent control, sh-RNF8 + solvent control, sh-NC + CDDP, and sh-RNF8 + CDDP. An inhibition experiment was conducted using the sh-RNF8 + CDDP + KU60019 combination. CCK-8 assays, colony formation assays, Annexin V-FITC/PI flow cytometry, Hoechst 33258/PI staining, WB, and γ-H2AX immunofluorescence were used to assess cell viability, colony formation, apoptosis, DNA damage, and the expression of proteins related to the ATM/CHK2 pathway. Results: RNF8 was significantly overexpressed in endometrial cancer tissues and cells. RNF8 knockdown reduced cell viability and IC50, inhibited colony formation, and further enhanced CDDP-induced apoptosis. Meanwhile, the expression of BAX, Cleaved-Caspase-3, and γ-H2AX increased, while the expression of BCL-2, p-ATM, p-CHK2, and RAD21 decreased. Treatment with KU60019 further promoted DNA damage and apoptosis, and reduced cell viability. Conclusion: RNF8 may promote DNA damage response and reduce the sensitivity of endometrial cancer cells to CDDP via the ATM/CHK2 axis. Knocking down RNF8 increases DNA damage and enhances sensitivity to CDDP.
2026, 33(8):840-847.
DOI: 10.3872/j.issn.1007-385X.2026.08.004
Abstract:
Objective: To investigate the conditions and mechanisms by which hypoxia induced the nuclear translocation of aconitase 2 (ACO2) and to explore the effects of ACO2 nuclear translocation on the proliferation, migration, and invasion of hepatocellular carcinoma PLC/PRF/5 cells. Methods: The expression and subcellular localization of ACO2 in human liver cancer tissues were analyzed using the Human Protein Atlas (HPA) database. The potential nuclear localization signal (NLS) of ACO2 was predicted by the NLStradamus website, and an NLS-deficient mutant gene (ACO2ΔNLS) was constructed using genetic engineering techniques. Wild-type (ACO2WT) and mutant (ACO2ΔNLS) plasmids were transfected into human hepatocellular carcinoma PLC/PRF/5 cells, and cells in each transfection group were then cultured under either normoxic or hypoxic (1% O?) conditions. The mechanisms underlying hypoxia-induced nuclear translocation of ACO2 were examined by immunofluorescence staining. The proliferation, migration, and invasion abilities of PLC/PRF/5 cells were assessed using EdU staining, wound healing assay, and Transwell invasion assay. The expression levels of ACO2 in nuclear and cytoplasmic fractions, as well as the levels of migration-and invasion-related proteins MMP2 and MMP9, were detected by WB. Results: HPA database analysis revealed high expression of ACO2 in both the nucleus and cytoplasm of liver cancer cells. Immunofluorescence staining and WB assay results demonstrated that hypoxia significantly induced the nuclear translocation of ACO2 in an NLS-dependent manner (all P < 0.01). Functional experiments showed that hypoxia-induced nuclear translocation of ACO2 further significantly enhanced the proliferation, migration (all P < 0.05), and invasion (all P < 0.05) abilities of PLC/PRF/5 cells. WB analysis indicated that ACO2 nuclear translocation up-regulated the expression levels of migration-and invasion-related proteins MMP2 and MMP9 (all P < 0.05). Conclusion: Hypoxia could induce the nuclear translocation of ACO2 in an NLS-dependent manner, thereby promoting the proliferation, migration, and invasion abilities of PLC/PRF/5 cells.
Objective: To investigate the conditions and mechanisms by which hypoxia induced the nuclear translocation of aconitase 2 (ACO2) and to explore the effects of ACO2 nuclear translocation on the proliferation, migration, and invasion of hepatocellular carcinoma PLC/PRF/5 cells. Methods: The expression and subcellular localization of ACO2 in human liver cancer tissues were analyzed using the Human Protein Atlas (HPA) database. The potential nuclear localization signal (NLS) of ACO2 was predicted by the NLStradamus website, and an NLS-deficient mutant gene (ACO2ΔNLS) was constructed using genetic engineering techniques. Wild-type (ACO2WT) and mutant (ACO2ΔNLS) plasmids were transfected into human hepatocellular carcinoma PLC/PRF/5 cells, and cells in each transfection group were then cultured under either normoxic or hypoxic (1% O?) conditions. The mechanisms underlying hypoxia-induced nuclear translocation of ACO2 were examined by immunofluorescence staining. The proliferation, migration, and invasion abilities of PLC/PRF/5 cells were assessed using EdU staining, wound healing assay, and Transwell invasion assay. The expression levels of ACO2 in nuclear and cytoplasmic fractions, as well as the levels of migration-and invasion-related proteins MMP2 and MMP9, were detected by WB. Results: HPA database analysis revealed high expression of ACO2 in both the nucleus and cytoplasm of liver cancer cells. Immunofluorescence staining and WB assay results demonstrated that hypoxia significantly induced the nuclear translocation of ACO2 in an NLS-dependent manner (all P < 0.01). Functional experiments showed that hypoxia-induced nuclear translocation of ACO2 further significantly enhanced the proliferation, migration (all P < 0.05), and invasion (all P < 0.05) abilities of PLC/PRF/5 cells. WB analysis indicated that ACO2 nuclear translocation up-regulated the expression levels of migration-and invasion-related proteins MMP2 and MMP9 (all P < 0.05). Conclusion: Hypoxia could induce the nuclear translocation of ACO2 in an NLS-dependent manner, thereby promoting the proliferation, migration, and invasion abilities of PLC/PRF/5 cells.
2026, 33(8):848-856.
DOI: 10.3872/j.issn.1007-385X.2026.08.005
Abstract:
Objective: To investigate the antitumor effects and potential mechanisms of the β-catenin/CREB-binding protein (CBP) pathway inhibitor PRI-724 combined with imatinib in BCR-ABL1-positive chronic myeloid leukemia (CML) cells and xenograft models. Methods: Human K562 cells and murine 32D myeloid cells stably expressing wild-type BCR-ABL1 (32D-WT) or T315I-mutant BCR-ABL1 (32D-T315I) were used for in vitro experiments. The effects of imatinib, PRI-724, and their combination on cell viability were detected using the CCK-8 assay, and the half-maximal inhibitory concentration (IC50) and combination index (CI) were calculated. Senescence-associated phenotypes were examined by SA-β-gal staining. Co-immunoprecipitation (Co-IP) was used to detect the effect of PRI-724 on the interaction between β-catenin and CBP/p300. For in vivo experiments, subcutaneous xenograft models were established in nude mice using K562, 32D-WT, and 32D-T315I cells. Untreated, imatinib, PRI?724, and imatinib + PRI?724 groups were established, and each group received the corresponding treatment, and tumor growth was monitored. The in vivo CI was calculated based on tumor growth inhibition (TGI). WB was used to detect the expression of PI3K/AKT signaling pathway-related proteins, nuclear β-catenin/CBP, and downstream effectors c-Myc and Cyclin D1 in tumor tissues. Results: Imatinib and PRI-724 inhibited K562, 32D-WT, and 32D-T315I cells in a concentration-dependent manner. The IC50 values of imatinib in K562, 32D-WT, and 32D- T315I cells were 0.860, 0.594, and 1.646 μmol/L, respectively; the IC50 values of PRI-724 in the above three cell types were 1.120, 0.761, and 0.756 μmol/L, respectively. Compared with 32D-WT cells, 32D-T315I cells showed reduced sensitivity to imatinib, whereas no obvious decrease in sensitivity to PRI-724 was observed. The CI values of imatinib + PRI-724 in K562, 32D-WT, and 32D-T315I cells were 0.635, 0.780, and 0.689, respectively, suggesting a synergistic inhibitory effect in vitro. SA- β-gal staining showed that, compared with imatinib monotherapy, PRI-724 monotherapy increased the proportion of SA- β-gal-positive cells in all three cell models, and the combination further increased this proportion. Co-IP results showed that, after PRI-724 treatment, the level of CBP co-precipitated with β-catenin was decreased, whereas the level of p300 co-precipitated with β-catenin was increased. In vivo experiments showed that, compared with the imatinib monotherapy group, the imatinib + PRI-724 combination group showed further reductions in tumor volume and tumor weight. However, the in vivo CI values calculated using the TGI-based response-additivity approach in the K562, 32D-WT, and 32D-T315I xenograft models were all > 1, suggesting that, under the current dose and administration regimen, the in vivo combination effect of the two drugs did not reach the expected additive effect and may have shown an antagonistic trend. WB showed that, compared with the imatinib monotherapy group, the combination treatment group had lower p-PI3K/PI3K and p-AKT/ AKT ratios and lower expression levels of nuclear β-catenin, CBP, c-Myc, and Cyclin D1 in tumor tissues. Conclusion: PRI-724 combined with imatinib exhibits a synergistic inhibitory effect in vitro and further suppresses tumor growth in vivo compared with imatinib monotherapy. The underlying mechanism may be related to modulation of the β-catenin/CBP/p300 complex, inhibition of the PI3K/AKT signaling pathway, and downregulation of c-Myc and Cyclin D1 expression.
Objective: To investigate the antitumor effects and potential mechanisms of the β-catenin/CREB-binding protein (CBP) pathway inhibitor PRI-724 combined with imatinib in BCR-ABL1-positive chronic myeloid leukemia (CML) cells and xenograft models. Methods: Human K562 cells and murine 32D myeloid cells stably expressing wild-type BCR-ABL1 (32D-WT) or T315I-mutant BCR-ABL1 (32D-T315I) were used for in vitro experiments. The effects of imatinib, PRI-724, and their combination on cell viability were detected using the CCK-8 assay, and the half-maximal inhibitory concentration (IC50) and combination index (CI) were calculated. Senescence-associated phenotypes were examined by SA-β-gal staining. Co-immunoprecipitation (Co-IP) was used to detect the effect of PRI-724 on the interaction between β-catenin and CBP/p300. For in vivo experiments, subcutaneous xenograft models were established in nude mice using K562, 32D-WT, and 32D-T315I cells. Untreated, imatinib, PRI?724, and imatinib + PRI?724 groups were established, and each group received the corresponding treatment, and tumor growth was monitored. The in vivo CI was calculated based on tumor growth inhibition (TGI). WB was used to detect the expression of PI3K/AKT signaling pathway-related proteins, nuclear β-catenin/CBP, and downstream effectors c-Myc and Cyclin D1 in tumor tissues. Results: Imatinib and PRI-724 inhibited K562, 32D-WT, and 32D-T315I cells in a concentration-dependent manner. The IC50 values of imatinib in K562, 32D-WT, and 32D- T315I cells were 0.860, 0.594, and 1.646 μmol/L, respectively; the IC50 values of PRI-724 in the above three cell types were 1.120, 0.761, and 0.756 μmol/L, respectively. Compared with 32D-WT cells, 32D-T315I cells showed reduced sensitivity to imatinib, whereas no obvious decrease in sensitivity to PRI-724 was observed. The CI values of imatinib + PRI-724 in K562, 32D-WT, and 32D-T315I cells were 0.635, 0.780, and 0.689, respectively, suggesting a synergistic inhibitory effect in vitro. SA- β-gal staining showed that, compared with imatinib monotherapy, PRI-724 monotherapy increased the proportion of SA- β-gal-positive cells in all three cell models, and the combination further increased this proportion. Co-IP results showed that, after PRI-724 treatment, the level of CBP co-precipitated with β-catenin was decreased, whereas the level of p300 co-precipitated with β-catenin was increased. In vivo experiments showed that, compared with the imatinib monotherapy group, the imatinib + PRI-724 combination group showed further reductions in tumor volume and tumor weight. However, the in vivo CI values calculated using the TGI-based response-additivity approach in the K562, 32D-WT, and 32D-T315I xenograft models were all > 1, suggesting that, under the current dose and administration regimen, the in vivo combination effect of the two drugs did not reach the expected additive effect and may have shown an antagonistic trend. WB showed that, compared with the imatinib monotherapy group, the combination treatment group had lower p-PI3K/PI3K and p-AKT/ AKT ratios and lower expression levels of nuclear β-catenin, CBP, c-Myc, and Cyclin D1 in tumor tissues. Conclusion: PRI-724 combined with imatinib exhibits a synergistic inhibitory effect in vitro and further suppresses tumor growth in vivo compared with imatinib monotherapy. The underlying mechanism may be related to modulation of the β-catenin/CBP/p300 complex, inhibition of the PI3K/AKT signaling pathway, and downregulation of c-Myc and Cyclin D1 expression.
2026, 33(8):857-866.
DOI: 10.3872/j.issn.1007-385X.2026.08.006
Abstract:
Objective: This study aimed to investigate the effects of miR-532-3p on thyroid cancer TPC-1 cell proliferation and glycolysis and to preliminarily explore the underlying mechanism by targeting dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST). Methods: The basal expression of miR-532-3p was assessed in normal thyroid Nthy-ori 3-1 cells and thyroid cancer cell lines TPC-1, FTC-133, and IHH-4. TPC-1 cells were selected for subsequent experiments and divided into mimic-NC group, miR-532-3p mimic group, inhibitor-NC group, miR-532-3p inhibitor group, mimic-NC + pcDNA-NC group, mimic-NC+pcDNA-DDOST group, miR-532-3p mimic + pcDNA-NC group, and miR-532-3p mimic + pcDNA-DDOST group. The targeting relationship between miR-532-3p and DDOST was detected by dual-luciferase reporter gene assay. Cell proliferation was detected by the CCK-8 method. Gene and protein expression levels were detected by reverse transcription quantitative PCR (RT-qPCR) and Western blotting. The TPC-1 cells were subcutaneously injected into the right posterior axillary region of nude mice to establish a xenograft tumor model of thyroid carcinoma, and the growth status of the tumors was recorded. Ki-67 and DDOST expression in xenograft tumor tissues was detected by immunohistochemistry. Lactate concentration and glucose consumption were measured using the corresponding assay kits. Results: Compared with normal thyroid cells Nthy-ori 3-1, the expression levels of miR-532-3p in thyroid cancer cell lines (TPC-1, FTC-133, IHH-4) were significantly decreased (P < 0.05), with the lowest level observed in TPC-1 cells. The expression of DDOST was significantly increased (P < 0.05). Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis and downregulated DDOST expression (P < 0.05). Moreover, these effects were reversed by DDOST overexpression (P < 0.05). Overexpression of miR-532-3p inhibited thyroid cancer xenograft growth and reduced DDOST expression in xenograft tumor tissues (P < 0.05). Conclusion: Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis by targeting DDOST and suppressed thyroid cancer xenograft growth in nude mice.
Objective: This study aimed to investigate the effects of miR-532-3p on thyroid cancer TPC-1 cell proliferation and glycolysis and to preliminarily explore the underlying mechanism by targeting dolichyl-diphosphooligosaccharide protein glycosyltransferase non-catalytic subunit (DDOST). Methods: The basal expression of miR-532-3p was assessed in normal thyroid Nthy-ori 3-1 cells and thyroid cancer cell lines TPC-1, FTC-133, and IHH-4. TPC-1 cells were selected for subsequent experiments and divided into mimic-NC group, miR-532-3p mimic group, inhibitor-NC group, miR-532-3p inhibitor group, mimic-NC + pcDNA-NC group, mimic-NC+pcDNA-DDOST group, miR-532-3p mimic + pcDNA-NC group, and miR-532-3p mimic + pcDNA-DDOST group. The targeting relationship between miR-532-3p and DDOST was detected by dual-luciferase reporter gene assay. Cell proliferation was detected by the CCK-8 method. Gene and protein expression levels were detected by reverse transcription quantitative PCR (RT-qPCR) and Western blotting. The TPC-1 cells were subcutaneously injected into the right posterior axillary region of nude mice to establish a xenograft tumor model of thyroid carcinoma, and the growth status of the tumors was recorded. Ki-67 and DDOST expression in xenograft tumor tissues was detected by immunohistochemistry. Lactate concentration and glucose consumption were measured using the corresponding assay kits. Results: Compared with normal thyroid cells Nthy-ori 3-1, the expression levels of miR-532-3p in thyroid cancer cell lines (TPC-1, FTC-133, IHH-4) were significantly decreased (P < 0.05), with the lowest level observed in TPC-1 cells. The expression of DDOST was significantly increased (P < 0.05). Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis and downregulated DDOST expression (P < 0.05). Moreover, these effects were reversed by DDOST overexpression (P < 0.05). Overexpression of miR-532-3p inhibited thyroid cancer xenograft growth and reduced DDOST expression in xenograft tumor tissues (P < 0.05). Conclusion: Overexpression of miR-532-3p inhibited TPC-1 cell proliferation and glycolysis by targeting DDOST and suppressed thyroid cancer xenograft growth in nude mice.
2026, 33(8):867-875.
DOI: 10.3872/j.issn.1007-385X.2026.08.007
Abstract:
Objective: To investigate whether cytochrome c oxidase copper chaperone 17 (COX17) is involved in the inhibitory effects of demethylzeylasteral (DML) on the proliferation and invasion of gastric cancer cells. Methods: MGC-803 cells were treated with DML at 5, 10 and 20 μmol/L, and the effects of DML on cell proliferation and invasion were evaluated by manual cell counting and Transwell assay, respectively. Label-free quantitative proteomics was applied to compare the protein expression profiles between the DML-treated group and the DMSO group, and candidate proteins were screened by differential expression analysis combined with Gene Ontology (GO) functional enrichment analysis. The change in COX17 protein expression after DML treatment was verified by Western blotting. COX17-knockdown and COX17-overexpressing stable cell lines were constructed separately, and the effects of COX17 on the proliferation and invasion of MGC-803 cells were evaluated by cell counting and Transwell assay. Molecular docking and 50 ns molecular dynamics simulation were used to analyze the potential binding mode between DML and COX17 as well as the conformational stability of the complex. The role of COX17 in the DML-induced inhibition of cell proliferation and invasion was further evaluated by a COX17 overexpression rescue experiment. Results: DML significantly inhibited the proliferation and invasion of MGC-803 cells, and the inhibitory effect was progressively enhanced with increasing DML concentration (all P < 0.000 1). A total of 72 differentially expressed proteins were screened by proteomics, of which 21 were upregulated and 51 were downregulated. Based on these differential expression characteristics, the GO enrichment results and our previous findings, COX17 was selected for further validation. DML significantly downregulated COX17 protein expression in MGC-803 cells (P < 0.000 1). Knockdown of COX17 inhibited cell proliferation and invasion, whereas overexpression of COX17 promoted these malignant phenotypes. Molecular docking suggested that interactions such as hydrophobic contacts, hydrogen bonds and salt bridges might exist between DML and COX17, with a docking score of ?6.8 kcal/mol. Molecular dynamics simulation showed that the DML-COX17 complex tended to be relatively stable overall during the 50 ns simulation. Overexpression of COX17 partially attenuated the inhibitory effects of DML on the proliferation and invasion of MGC-803 cells (P < 0.01). Conclusion: DML can inhibit the proliferation and invasion of MGC-803 cells and downregulate COX17 protein expression, and COX17 may be involved in the regulation of the malignant phenotypes of gastric cancer cells by DML.
Objective: To investigate whether cytochrome c oxidase copper chaperone 17 (COX17) is involved in the inhibitory effects of demethylzeylasteral (DML) on the proliferation and invasion of gastric cancer cells. Methods: MGC-803 cells were treated with DML at 5, 10 and 20 μmol/L, and the effects of DML on cell proliferation and invasion were evaluated by manual cell counting and Transwell assay, respectively. Label-free quantitative proteomics was applied to compare the protein expression profiles between the DML-treated group and the DMSO group, and candidate proteins were screened by differential expression analysis combined with Gene Ontology (GO) functional enrichment analysis. The change in COX17 protein expression after DML treatment was verified by Western blotting. COX17-knockdown and COX17-overexpressing stable cell lines were constructed separately, and the effects of COX17 on the proliferation and invasion of MGC-803 cells were evaluated by cell counting and Transwell assay. Molecular docking and 50 ns molecular dynamics simulation were used to analyze the potential binding mode between DML and COX17 as well as the conformational stability of the complex. The role of COX17 in the DML-induced inhibition of cell proliferation and invasion was further evaluated by a COX17 overexpression rescue experiment. Results: DML significantly inhibited the proliferation and invasion of MGC-803 cells, and the inhibitory effect was progressively enhanced with increasing DML concentration (all P < 0.000 1). A total of 72 differentially expressed proteins were screened by proteomics, of which 21 were upregulated and 51 were downregulated. Based on these differential expression characteristics, the GO enrichment results and our previous findings, COX17 was selected for further validation. DML significantly downregulated COX17 protein expression in MGC-803 cells (P < 0.000 1). Knockdown of COX17 inhibited cell proliferation and invasion, whereas overexpression of COX17 promoted these malignant phenotypes. Molecular docking suggested that interactions such as hydrophobic contacts, hydrogen bonds and salt bridges might exist between DML and COX17, with a docking score of ?6.8 kcal/mol. Molecular dynamics simulation showed that the DML-COX17 complex tended to be relatively stable overall during the 50 ns simulation. Overexpression of COX17 partially attenuated the inhibitory effects of DML on the proliferation and invasion of MGC-803 cells (P < 0.01). Conclusion: DML can inhibit the proliferation and invasion of MGC-803 cells and downregulate COX17 protein expression, and COX17 may be involved in the regulation of the malignant phenotypes of gastric cancer cells by DML.
2026, 33(8):876-885.
DOI: 10.3872/j.issn.1007-385X.2026.08.008
Abstract:
Objective: This study aims to systematically characterize the unique DNA methylation landscape of breast cancer in young women (BCYW), identify prognosis-associated methylation loci, develop and externally validate a robust prognostic prediction model, and further elucidate its clinical utility via multi-omics integration analysis and protein-level validation of a pivotal candidate gene. Methods: DNA methylation and clinical data were obtained from The Cancer Genome Atlas (TCGA). BCYW?specific methylation loci were identified. A prognostic prediction model was developed using random forest, LASSO regression, and univariate and multivariate Cox regression analyses. The predictive performance of the constructed model was comprehensively evaluated using receiver operating characteristic (ROC) curves, calibration plots, and the concordance index (C-index). Multi?omics characteristics were compared between high?risk and low?risk subgroups. In an independent cohort, immunohistochemistry was performed to assess the association between LAMA5 protein expression and clinical outcomes. Results: Compared with their older counterparts with breast cancer, young patients exhibited prominent hypomethylation in promoter regions, which was particularly pronounced within CpG islands. Through a multi-step differential methylation analysis, a total of 3 489 BCYW?specific methylation loci were identified. Subsequent univariate and multivariate Cox regression analyses further screened out 12 loci that were independently correlated with overall survival (OS), among which 4 were located in promoter regions, 4 in gene body regions, and the remaining 4 in intergenic regions. The prognostic prediction model constructed based on these 12 methylation loci exhibited satisfactory discriminative performance in the TCGA training cohort, where patients assigned to the high-risk subgroup presented significantly worse overall survival outcomes (P = 0.002 5). The areas under the curve (AUCs) for 5?, 8?, and 10?year OS prediction ranged from 0.88 to 0.94. Multi?omics analysis revealed that the high?risk subgroup exhibited the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, higher frequency of TP53 mutations, and lower expression of estrogen receptor alpha protein. Incorporating key multi-omics indicators, including TP53 mutation status and estrogen receptor 1 (ESR1) mRNA expression level, into the comprehensive nomogram further significantly improved the model's predictive performance. Tissue microarray-based immunohistochemical validation demonstrated that young breast cancer patients with negative LAMA5 protein expression exhibited significantly shorter OS (P = 0.046), and this phenotype was enriched in triple-negative breast cancer, consistent with the clinicopathological features of the high-risk group defined by the methylation model. Conclusion: The 12-methylation-site model integrating promoter and non-promoter region information shows potential for prognostic stratification in young patients with breast cancer. The multi-omics nomogram constructed by combining age, TP53 mutations and ESR1 mRNA expression level demonstrated superior predictive performance over the methylation-only model.
Objective: This study aims to systematically characterize the unique DNA methylation landscape of breast cancer in young women (BCYW), identify prognosis-associated methylation loci, develop and externally validate a robust prognostic prediction model, and further elucidate its clinical utility via multi-omics integration analysis and protein-level validation of a pivotal candidate gene. Methods: DNA methylation and clinical data were obtained from The Cancer Genome Atlas (TCGA). BCYW?specific methylation loci were identified. A prognostic prediction model was developed using random forest, LASSO regression, and univariate and multivariate Cox regression analyses. The predictive performance of the constructed model was comprehensively evaluated using receiver operating characteristic (ROC) curves, calibration plots, and the concordance index (C-index). Multi?omics characteristics were compared between high?risk and low?risk subgroups. In an independent cohort, immunohistochemistry was performed to assess the association between LAMA5 protein expression and clinical outcomes. Results: Compared with their older counterparts with breast cancer, young patients exhibited prominent hypomethylation in promoter regions, which was particularly pronounced within CpG islands. Through a multi-step differential methylation analysis, a total of 3 489 BCYW?specific methylation loci were identified. Subsequent univariate and multivariate Cox regression analyses further screened out 12 loci that were independently correlated with overall survival (OS), among which 4 were located in promoter regions, 4 in gene body regions, and the remaining 4 in intergenic regions. The prognostic prediction model constructed based on these 12 methylation loci exhibited satisfactory discriminative performance in the TCGA training cohort, where patients assigned to the high-risk subgroup presented significantly worse overall survival outcomes (P = 0.002 5). The areas under the curve (AUCs) for 5?, 8?, and 10?year OS prediction ranged from 0.88 to 0.94. Multi?omics analysis revealed that the high?risk subgroup exhibited the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, higher frequency of TP53 mutations, and lower expression of estrogen receptor alpha protein. Incorporating key multi-omics indicators, including TP53 mutation status and estrogen receptor 1 (ESR1) mRNA expression level, into the comprehensive nomogram further significantly improved the model's predictive performance. Tissue microarray-based immunohistochemical validation demonstrated that young breast cancer patients with negative LAMA5 protein expression exhibited significantly shorter OS (P = 0.046), and this phenotype was enriched in triple-negative breast cancer, consistent with the clinicopathological features of the high-risk group defined by the methylation model. Conclusion: The 12-methylation-site model integrating promoter and non-promoter region information shows potential for prognostic stratification in young patients with breast cancer. The multi-omics nomogram constructed by combining age, TP53 mutations and ESR1 mRNA expression level demonstrated superior predictive performance over the methylation-only model.
2026, 33(8):886-898.
DOI: 10.3872/j.issn.1007-385X.2026.08.009
Abstract:
Objective: This study aimed to investigate the impact of peptidylarginine deiminase 1 (PADI1) on the migration, proliferation, and invasion of clear cell renal cell carcinoma (ccRCC) cells and the related molecular mechanisms. Methods: Differentially expressed genes between ccRCC and adjacent normal tissues were screened using transcriptome sequencing, and their expression levels were analyzed via GEPIA, TIMER2.0, and other bioinformatics platforms. A total of 59 ccRCC specimens were obtained from patients who underwent nephrectomy at the Department of Urology, The Fourth Hospital of Hebei Medical University between 2024 and 2025. The expression levels of PADI1 in cancerous and adjacent tissues were measured by RT-qPCR and immunohistochemistry (SP method), and their correlations with various clinicopathological parameters were analyzed. The effects of PADI1 on migration, proliferation, and invasion of ccRCC cells were evaluated by wound-healing, CCK-8, colony formation, and Transwell assays. Flow cytometry was used to examine the effects of PADI1 on cell cycle, and Western blotting was employed to detect changes in the expression levels of proteins related to the cornified envelope (CE) formation pathway and epithelial-mesenchymal transition (EMT) in the transfected A498 cells. Results: The relative expression level of PADI1 in ccRCC tissues was significantly higher than that in adjacent normal tissues (P < 0.01), and was correlated with patient age, lymph node metastasis, distant metastasis, and clinical stage (P < 0.05). Transfection of A498 and ACHN cells with si-PADI1 effectively down-regulated PADI1 mRNA and protein expression (P < 0.05), whereas transfection with overexpression plasmid significantly up-regulated its expression (P < 0.05). Knockdown of PADI1 significantly inhibited cell migration (P < 0.05), proliferation (P < 0.05), and invasion (P < 0.001), while PADI1 overexpression enhanced these abilities (P < 0.05, P < 0.05, and P < 0.001), whereas no significant effect on cell cycle progression was detected. Western blotting results showed that altered PADI1 expression in A498 cells was accompanied by changes in the expression levels of proteins related to EMT and the CE formation pathway. Conclusion: PADI1 is highly expressed in ccRCC and associated with patient age, lymph node metastasis, distant metastasis, and clinical stage. Elevated PADI1 expression affects the CE formation pathway and accelerates EMT progression, thereby enhancing the migration, proliferation, and invasion of renal cancer cells.
Objective: This study aimed to investigate the impact of peptidylarginine deiminase 1 (PADI1) on the migration, proliferation, and invasion of clear cell renal cell carcinoma (ccRCC) cells and the related molecular mechanisms. Methods: Differentially expressed genes between ccRCC and adjacent normal tissues were screened using transcriptome sequencing, and their expression levels were analyzed via GEPIA, TIMER2.0, and other bioinformatics platforms. A total of 59 ccRCC specimens were obtained from patients who underwent nephrectomy at the Department of Urology, The Fourth Hospital of Hebei Medical University between 2024 and 2025. The expression levels of PADI1 in cancerous and adjacent tissues were measured by RT-qPCR and immunohistochemistry (SP method), and their correlations with various clinicopathological parameters were analyzed. The effects of PADI1 on migration, proliferation, and invasion of ccRCC cells were evaluated by wound-healing, CCK-8, colony formation, and Transwell assays. Flow cytometry was used to examine the effects of PADI1 on cell cycle, and Western blotting was employed to detect changes in the expression levels of proteins related to the cornified envelope (CE) formation pathway and epithelial-mesenchymal transition (EMT) in the transfected A498 cells. Results: The relative expression level of PADI1 in ccRCC tissues was significantly higher than that in adjacent normal tissues (P < 0.01), and was correlated with patient age, lymph node metastasis, distant metastasis, and clinical stage (P < 0.05). Transfection of A498 and ACHN cells with si-PADI1 effectively down-regulated PADI1 mRNA and protein expression (P < 0.05), whereas transfection with overexpression plasmid significantly up-regulated its expression (P < 0.05). Knockdown of PADI1 significantly inhibited cell migration (P < 0.05), proliferation (P < 0.05), and invasion (P < 0.001), while PADI1 overexpression enhanced these abilities (P < 0.05, P < 0.05, and P < 0.001), whereas no significant effect on cell cycle progression was detected. Western blotting results showed that altered PADI1 expression in A498 cells was accompanied by changes in the expression levels of proteins related to EMT and the CE formation pathway. Conclusion: PADI1 is highly expressed in ccRCC and associated with patient age, lymph node metastasis, distant metastasis, and clinical stage. Elevated PADI1 expression affects the CE formation pathway and accelerates EMT progression, thereby enhancing the migration, proliferation, and invasion of renal cancer cells.
2026, 33(8):899-908.
DOI: 10.3872/j.issn.1007-385X.2026.08.010
Abstract:
Objective: To investigate whether RNA binding motif protein 15 (RBM15) promotes cervical cancer cell proliferation, migration, and invasion through the transmembrane Bax inhibitor motif-containing 6 (TMBIM6)/TGF-β/Smad axis. Methods: Tumor tissues and adjacent tissues were collected from 82 cervical cancer patients who underwent surgical treatment at the Affiliated Zhangjiagang Hospital of Soochow University from January 2023 to January 2025. R was used to analyze RBM15 and TMBIM6 mRNA expression in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry and Western blotting assays were used to detect RBM15 and TMBIM6 protein expression. Kaplan-Meier curves were used to analyze the associations of RBM15 and TMBIM6 mRNA expression with the prognosis of patients with cervical cancer. Cell Counting Kit-8 (CCK-8), scratch, and Transwell invasion assays were used to evaluate the effects of RBM15 and TMBIM6 on cervical cancer cell proliferation, migration, and invasion. The sequence-based RNA adenosine methylation site predictor (SRAMP) was used to predict N6-methyladenosine (m6A) modification sites in TMBIM6 mRNA. RNA immunoprecipitation (RIP), RNA decay, and rescue assays were performed to investigate the interaction between RBM15 and TMBIM6 mRNA. Methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR) was used to detect m6A enrichment in TMBIM6 mRNA. Western blotting assays were used to assess the effects of RBM15 and TMBIM6 on TGF-β/Smad pathway-related protein expression. Results: RBM15 and TMBIM6 mRNA expression levels in cervical cancer tissues were higher than those in adjacent noncancerous tissues (both P < 0.05), and the positivity rates of RBM15 and TMBIM6 were higher in cancer tissues than in adjacent noncancerous tissues (both P < 0.001). RBM15 and TMBIM6 protein expression levels in HeLa, MS-751, and SiHa cells were higher than those in Ect1/E6E7 cells (all P < 0.05). The positivity rates of RBM15 and TMBIM6 in cervical cancer tissues at FIGO stages IB2-IIB were higher than those at stages IA-IB1 (both P < 0.05). The 5-year progression-free survival rates in the RBM15 and TMBIM6 high-expression groups were lower than those in their respective low-expression groups (both P < 0.05). RBM15 mRNA expression was positively correlated with TMBIM6 mRNA expression in cervical cancer tissues (P < 0.05). SRAMP predicted high-confidence m6A modification sites at positions 960, 24876, and 25203 in TMBIM6 mRNA. RBM15 overexpression increased, whereas RBM15 knockdown decreased, TMBIM6 mRNA and protein expression in HeLa and SiHa cells (P < 0.05). TMBIM6 mRNA was significantly enriched in RBM15 immunoprecipitates compared with the IgG group. MeRIP-qPCR showed significant m6A enrichment at positions 960, 24876, and 25203 of TMBIM6 mRNA. RBM15 knockdown shortened the half-life and reduced the stability of TMBIM6 mRNA. RBM15 knockdown inhibited cervical cancer cell proliferation, migration, and invasion, whereas TMBIM6 overexpression reversed these effects. TMBIM6 overexpression increased TGF-β1, Smad2, and Smad3 protein expression, whereas RBM15 knockdown decreased their expression; TMBIM6 overexpression reversed the effects of RBM15 knockdown. Conclusion: The results suggest that RBM15 may increase TMBIM6 mRNA stability through m6A modification and activate the TGF-β/Smad pathway, thereby promoting cervical cancer cell proliferation, migration, and invasion.
Objective: To investigate whether RNA binding motif protein 15 (RBM15) promotes cervical cancer cell proliferation, migration, and invasion through the transmembrane Bax inhibitor motif-containing 6 (TMBIM6)/TGF-β/Smad axis. Methods: Tumor tissues and adjacent tissues were collected from 82 cervical cancer patients who underwent surgical treatment at the Affiliated Zhangjiagang Hospital of Soochow University from January 2023 to January 2025. R was used to analyze RBM15 and TMBIM6 mRNA expression in The Cancer Genome Atlas (TCGA) database. Immunohistochemistry and Western blotting assays were used to detect RBM15 and TMBIM6 protein expression. Kaplan-Meier curves were used to analyze the associations of RBM15 and TMBIM6 mRNA expression with the prognosis of patients with cervical cancer. Cell Counting Kit-8 (CCK-8), scratch, and Transwell invasion assays were used to evaluate the effects of RBM15 and TMBIM6 on cervical cancer cell proliferation, migration, and invasion. The sequence-based RNA adenosine methylation site predictor (SRAMP) was used to predict N6-methyladenosine (m6A) modification sites in TMBIM6 mRNA. RNA immunoprecipitation (RIP), RNA decay, and rescue assays were performed to investigate the interaction between RBM15 and TMBIM6 mRNA. Methylated RNA immunoprecipitation quantitative PCR (MeRIP-qPCR) was used to detect m6A enrichment in TMBIM6 mRNA. Western blotting assays were used to assess the effects of RBM15 and TMBIM6 on TGF-β/Smad pathway-related protein expression. Results: RBM15 and TMBIM6 mRNA expression levels in cervical cancer tissues were higher than those in adjacent noncancerous tissues (both P < 0.05), and the positivity rates of RBM15 and TMBIM6 were higher in cancer tissues than in adjacent noncancerous tissues (both P < 0.001). RBM15 and TMBIM6 protein expression levels in HeLa, MS-751, and SiHa cells were higher than those in Ect1/E6E7 cells (all P < 0.05). The positivity rates of RBM15 and TMBIM6 in cervical cancer tissues at FIGO stages IB2-IIB were higher than those at stages IA-IB1 (both P < 0.05). The 5-year progression-free survival rates in the RBM15 and TMBIM6 high-expression groups were lower than those in their respective low-expression groups (both P < 0.05). RBM15 mRNA expression was positively correlated with TMBIM6 mRNA expression in cervical cancer tissues (P < 0.05). SRAMP predicted high-confidence m6A modification sites at positions 960, 24876, and 25203 in TMBIM6 mRNA. RBM15 overexpression increased, whereas RBM15 knockdown decreased, TMBIM6 mRNA and protein expression in HeLa and SiHa cells (P < 0.05). TMBIM6 mRNA was significantly enriched in RBM15 immunoprecipitates compared with the IgG group. MeRIP-qPCR showed significant m6A enrichment at positions 960, 24876, and 25203 of TMBIM6 mRNA. RBM15 knockdown shortened the half-life and reduced the stability of TMBIM6 mRNA. RBM15 knockdown inhibited cervical cancer cell proliferation, migration, and invasion, whereas TMBIM6 overexpression reversed these effects. TMBIM6 overexpression increased TGF-β1, Smad2, and Smad3 protein expression, whereas RBM15 knockdown decreased their expression; TMBIM6 overexpression reversed the effects of RBM15 knockdown. Conclusion: The results suggest that RBM15 may increase TMBIM6 mRNA stability through m6A modification and activate the TGF-β/Smad pathway, thereby promoting cervical cancer cell proliferation, migration, and invasion.
2026, 33(8):909-915.
DOI: 10.3872/j.issn.1007-385X.2026.08.011
Abstract:
目的：基于双向两样本孟德尔随机化（MR）设计，系统评估遗传预测的肥胖相关指标[体重指数（BMI）和体重]及血脂指标[高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）]与淋巴瘤及其主要亚型发病风险的因果关联，并探索潜在的反向因果关系。方法：基于IEU OpenGWAS数据库中肥胖及血脂相关指标和FinnGen数据库中淋巴瘤及其主要亚型的全基因组关联研究汇总数据开展分析。筛选显著性水平为P < 1 × 10??的独立遗传变异作为工具变量，经连锁不平衡剔除、等位基因对齐和回文序列排除后，以逆方差加权（IVW）法为主要因果效应分析方法，辅以加权中位数法和MR-Egger回归进行敏感性分析；采用Cochran's Q检验、MR-Egger截距检验及留一法评估结果的异质性、水平多效性和稳健性，并评估反向MR分析的可行性。结果：IVW分析显示，以比值比（OR）及95%置信区间（CI）表示效应量时，遗传预测的体重升高与非霍奇金淋巴瘤（NHL）（OR =1.32，95% CI：1.14～1.52，P < 0.001）、霍奇金淋巴瘤（HL）（OR = 1.55，95% CI：1.16～2.06，P < 0.001）、滤泡性淋巴瘤（FL）（OR =1.37，95% CI：1.06～1.76，P = 0.014）和弥漫大B细胞淋巴瘤（DLBCL）（OR = 1.29，95% CI：1.02～1.62，P = 0.033）发病风险升高显著相关；与T/NK细胞淋巴瘤发病风险无显著因果关联。遗传预测的BMI升高与NHL（OR = 1.20，95% CI：1.05～1.36，P < 0.001）和HL（OR = 1.32，95% CI：1.01～1.74，P = 0.042）发病风险呈显著正相关。HDL-C、LDL-C与淋巴瘤各亚型发病风险均无显著因果关联（均P > 0.05）。敏感性分析结果与主分析方向一致，整体结果较为稳健。反向MR分析因有效独立工具变量不足，未能获得稳定的因果效应估计。结论：本研究为体重升高与NHL、HL、FL及DLBCL风险升高，以及BMI升高与NHL、HL风险升高的关联提供了遗传学证据；未提示血脂指标与淋巴瘤发病存在显著因果关联。结果提示肥胖可能参与淋巴瘤的发生，可为相关病因学研究和风险评估提供参考。
目的：基于双向两样本孟德尔随机化（MR）设计，系统评估遗传预测的肥胖相关指标[体重指数（BMI）和体重]及血脂指标[高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）]与淋巴瘤及其主要亚型发病风险的因果关联，并探索潜在的反向因果关系。方法：基于IEU OpenGWAS数据库中肥胖及血脂相关指标和FinnGen数据库中淋巴瘤及其主要亚型的全基因组关联研究汇总数据开展分析。筛选显著性水平为P < 1 × 10??的独立遗传变异作为工具变量，经连锁不平衡剔除、等位基因对齐和回文序列排除后，以逆方差加权（IVW）法为主要因果效应分析方法，辅以加权中位数法和MR-Egger回归进行敏感性分析；采用Cochran's Q检验、MR-Egger截距检验及留一法评估结果的异质性、水平多效性和稳健性，并评估反向MR分析的可行性。结果：IVW分析显示，以比值比（OR）及95%置信区间（CI）表示效应量时，遗传预测的体重升高与非霍奇金淋巴瘤（NHL）（OR =1.32，95% CI：1.14～1.52，P < 0.001）、霍奇金淋巴瘤（HL）（OR = 1.55，95% CI：1.16～2.06，P < 0.001）、滤泡性淋巴瘤（FL）（OR =1.37，95% CI：1.06～1.76，P = 0.014）和弥漫大B细胞淋巴瘤（DLBCL）（OR = 1.29，95% CI：1.02～1.62，P = 0.033）发病风险升高显著相关；与T/NK细胞淋巴瘤发病风险无显著因果关联。遗传预测的BMI升高与NHL（OR = 1.20，95% CI：1.05～1.36，P < 0.001）和HL（OR = 1.32，95% CI：1.01～1.74，P = 0.042）发病风险呈显著正相关。HDL-C、LDL-C与淋巴瘤各亚型发病风险均无显著因果关联（均P > 0.05）。敏感性分析结果与主分析方向一致，整体结果较为稳健。反向MR分析因有效独立工具变量不足，未能获得稳定的因果效应估计。结论：本研究为体重升高与NHL、HL、FL及DLBCL风险升高，以及BMI升高与NHL、HL风险升高的关联提供了遗传学证据；未提示血脂指标与淋巴瘤发病存在显著因果关联。结果提示肥胖可能参与淋巴瘤的发生，可为相关病因学研究和风险评估提供参考。
2026, 33(8):916-921.
DOI: 10.3872/j.issn.1007-385X.2026.08.012
Abstract:
FGF/FGFR信号通路是调控细胞生长、分化与增殖的核心通路，其异常激活是驱动肿瘤发生发展的重要机制。该通路通过激活MAPK、PLCγ-PKC等下游信号，广泛参与肿瘤细胞的增殖、存活、侵袭、代谢重编程及肿瘤微环境重塑等过程。近年来，以酪氨酸激酶抑制剂（TKI）、单克隆抗体和FGF配体陷阱分子为代表的FGF/FGFR靶向治疗策略，在临床前研究与临床试验中展现出显著疗效，厄达替尼等药物已成功应用于特定肿瘤的临床治疗。鉴于FGF/FGFR通路在肿瘤生物学中的核心地位及其功能多样性，开发新一代高效靶向抑制剂的重要性不言而喻。本综述阐释了FGF/FGFR信号在肿瘤中的多维作用机制，总结了靶向治疗的最新进展，深入探讨了其耐药机制与联合治疗策略，并对该领域未来的转化研究方向进行了展望，以期为FGF/FGFR靶向药物的研发与个体化治疗提供理论依据。
FGF/FGFR信号通路是调控细胞生长、分化与增殖的核心通路，其异常激活是驱动肿瘤发生发展的重要机制。该通路通过激活MAPK、PLCγ-PKC等下游信号，广泛参与肿瘤细胞的增殖、存活、侵袭、代谢重编程及肿瘤微环境重塑等过程。近年来，以酪氨酸激酶抑制剂（TKI）、单克隆抗体和FGF配体陷阱分子为代表的FGF/FGFR靶向治疗策略，在临床前研究与临床试验中展现出显著疗效，厄达替尼等药物已成功应用于特定肿瘤的临床治疗。鉴于FGF/FGFR通路在肿瘤生物学中的核心地位及其功能多样性，开发新一代高效靶向抑制剂的重要性不言而喻。本综述阐释了FGF/FGFR信号在肿瘤中的多维作用机制，总结了靶向治疗的最新进展，深入探讨了其耐药机制与联合治疗策略，并对该领域未来的转化研究方向进行了展望，以期为FGF/FGFR靶向药物的研发与个体化治疗提供理论依据。
2026, 33(8):922-928.
DOI: 10.3872/j.issn.1007-385X.2026.08.013
Abstract:
肿瘤免疫微环境重塑是驱动非小细胞肺癌（NSCLC）恶性进展及治疗抵抗的核心机制。中性粒细胞胞外陷阱（NET）作为肿瘤微环境的关键组分，在NSCLC中异常富集，并通过调控免疫细胞功能影响肿瘤进展与治疗应答。本文系统综述NET的生物学基础及其在NSCLC中的分布特征，重点阐述其诱导T细胞耗竭、巨噬细胞M2型极化、自然杀伤细胞（NK）功能抑制及介导免疫治疗耐药的分子机制。同时，本文总结了基于NET的预后评估模型及靶向治疗策略的研究进展，探讨了NET作为联合免疫治疗新靶点的临床转化潜力，旨在为优化NSCLC精准免疫治疗策略提供理论依据。
肿瘤免疫微环境重塑是驱动非小细胞肺癌（NSCLC）恶性进展及治疗抵抗的核心机制。中性粒细胞胞外陷阱（NET）作为肿瘤微环境的关键组分，在NSCLC中异常富集，并通过调控免疫细胞功能影响肿瘤进展与治疗应答。本文系统综述NET的生物学基础及其在NSCLC中的分布特征，重点阐述其诱导T细胞耗竭、巨噬细胞M2型极化、自然杀伤细胞（NK）功能抑制及介导免疫治疗耐药的分子机制。同时，本文总结了基于NET的预后评估模型及靶向治疗策略的研究进展，探讨了NET作为联合免疫治疗新靶点的临床转化潜力，旨在为优化NSCLC精准免疫治疗策略提供理论依据。
2026, 33(8):929-934.
DOI: 10.3872/j.issn.1007-385X.2026.08.014
Abstract:
脊索瘤是一种低度恶性的原发性骨肿瘤，对传统放化疗不敏感且术后复发率较高，现有治疗策略存在明显局限，亟需探索新的治疗策略。生物治疗被视为突破口，具有广阔的研究前景。本文主要介绍生物治疗策略在脊索瘤中的应用现状，包括针对不同生长因子相关信号通路的靶向疗法，以及肿瘤疫苗、嵌合抗原受体T细胞疗法、溶瘤病毒疗法和免疫检查点抑制剂疗法等免疫疗法。其中，靶向疗法疗效已在临床研究阶段初步验证；肿瘤疫苗安全性良好；嵌合抗原受体T细胞疗法及溶瘤病毒疗法目前主要处于临床前或早期临床探索阶段，其疗效尚待进一步验证；免疫检查点抑制剂疗法在复发性脊索瘤中显示出一定临床活性，但其治疗定位仍需前瞻性研究进一步验证。未来通过对不同疗法进行有效联合并加以完善，有望在降低脊索瘤复发风险、提高总体疗效等方面发挥重要作用。本文针对不同疗法的作用机制、疗效、研究进展及目前存在的问题进行阐述，并提出可能的解决对策；通过对现有方案的对比分析，为脊索瘤的治疗研究提供参考。
脊索瘤是一种低度恶性的原发性骨肿瘤，对传统放化疗不敏感且术后复发率较高，现有治疗策略存在明显局限，亟需探索新的治疗策略。生物治疗被视为突破口，具有广阔的研究前景。本文主要介绍生物治疗策略在脊索瘤中的应用现状，包括针对不同生长因子相关信号通路的靶向疗法，以及肿瘤疫苗、嵌合抗原受体T细胞疗法、溶瘤病毒疗法和免疫检查点抑制剂疗法等免疫疗法。其中，靶向疗法疗效已在临床研究阶段初步验证；肿瘤疫苗安全性良好；嵌合抗原受体T细胞疗法及溶瘤病毒疗法目前主要处于临床前或早期临床探索阶段，其疗效尚待进一步验证；免疫检查点抑制剂疗法在复发性脊索瘤中显示出一定临床活性，但其治疗定位仍需前瞻性研究进一步验证。未来通过对不同疗法进行有效联合并加以完善，有望在降低脊索瘤复发风险、提高总体疗效等方面发挥重要作用。本文针对不同疗法的作用机制、疗效、研究进展及目前存在的问题进行阐述，并提出可能的解决对策；通过对现有方案的对比分析，为脊索瘤的治疗研究提供参考。
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- 《中国肿瘤生物治疗杂志》
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