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Volume 28,Issue 1,2021 Table of Contents
2021, 28(1):1-10.
DOI: 10.3872/j.issn.1007-385X.2021.01.001
Abstract:
With the development of new technology and the innovation of research mode, tumor immunological research has achieved rapid development, and tumor immunotherapy has also shown remarkable clinical efficacy, jointly promoting the improvement of tumor immunology from mechanism research to clinical transformation and from single discipline to multi-disciplinary integration. However,multiple challenges still exist in tumor immunological research, such as the animal model replication for clinical tumor study, the complexity of tumor intrinsic regulation and its relationship with host microenvironment, and the screening of immunotherapy targets and the prediction of treatment effect. These problems limit the further development and application of tumor immunology, but also bring research opportunities to basic and clinical immunology researchers. Therefore, this review summarizes the research status and challenges as well as looks into the future of tumor immunity and immunotherapy in five aspects: the change of research model,the innovation of mechanism, the exploration of research objects, the screening and evaluation of therapeutic targets, as well as the application and innovation of new technologies.
With the development of new technology and the innovation of research mode, tumor immunological research has achieved rapid development, and tumor immunotherapy has also shown remarkable clinical efficacy, jointly promoting the improvement of tumor immunology from mechanism research to clinical transformation and from single discipline to multi-disciplinary integration. However,multiple challenges still exist in tumor immunological research, such as the animal model replication for clinical tumor study, the complexity of tumor intrinsic regulation and its relationship with host microenvironment, and the screening of immunotherapy targets and the prediction of treatment effect. These problems limit the further development and application of tumor immunology, but also bring research opportunities to basic and clinical immunology researchers. Therefore, this review summarizes the research status and challenges as well as looks into the future of tumor immunity and immunotherapy in five aspects: the change of research model,the innovation of mechanism, the exploration of research objects, the screening and evaluation of therapeutic targets, as well as the application and innovation of new technologies.
2021, 28(1):11-16.
DOI: 10.3872/j.issn.1007-385X.2021.01.002
Abstract:
Objective: To explore the anti-tumor activity of oncolytic adenovirus co-expressing lymphocyte activation gene 3 (LAG-3)antibody (aLAG) against glioblastoma. Methods: aLAG sequence was inserted into the skeleton of oncolytic adenovirus Ad3 to obtain recombinant oncolytic adenovirus (Ad3-aLAG). The expression of aLAG in infected gliblastoma GL261 cells was detected by WB. The cytotoxicity of recombinant oncolytic adenovirus against glioblastoma was detected by MTT method. The tumor inhibitory activity of recombinant oncolytic adenovirus against glioblastoma in vivo was evaluated with mice subcutaneous xenograft model. Tumor infiltrating T cells were detected by immunohistochemical staining, and the levels of cytokines TNF-α and IFN-γ secreted by tumor infiltrating T cells were detected by Flow cytometry. Results: The recombinant oncolytic adenovirus was successfully constructed,which could effectively express aLAG and kill GL261 cells in vitro (all P<0.01). Experimental results of mice subcutaneous xenograft model showed that the tumor inhibition ability of recombinant oncolytic adenovirus Ad3-aLAG was stronger than that of Ad3 oncolytic adenovirus (P<0.01), and Ad3-aLAG could effectively enhance the infiltration of CD3+T cells in tumor tissue (P<0.01) and enhance the IFN- γ secretion ability of infiltrating T cells (P<0.01). Conclusion: Ad3-aLAG recombinant oncolytic adenovirus can significantly inhibit the growth of glioblastoma cells in vivo and in vitro, and enhance the anti-tumor immune response in vivo, which is promising to provide a new scheme for the treatment of glioblastoma.
Objective: To explore the anti-tumor activity of oncolytic adenovirus co-expressing lymphocyte activation gene 3 (LAG-3)antibody (aLAG) against glioblastoma. Methods: aLAG sequence was inserted into the skeleton of oncolytic adenovirus Ad3 to obtain recombinant oncolytic adenovirus (Ad3-aLAG). The expression of aLAG in infected gliblastoma GL261 cells was detected by WB. The cytotoxicity of recombinant oncolytic adenovirus against glioblastoma was detected by MTT method. The tumor inhibitory activity of recombinant oncolytic adenovirus against glioblastoma in vivo was evaluated with mice subcutaneous xenograft model. Tumor infiltrating T cells were detected by immunohistochemical staining, and the levels of cytokines TNF-α and IFN-γ secreted by tumor infiltrating T cells were detected by Flow cytometry. Results: The recombinant oncolytic adenovirus was successfully constructed,which could effectively express aLAG and kill GL261 cells in vitro (all P<0.01). Experimental results of mice subcutaneous xenograft model showed that the tumor inhibition ability of recombinant oncolytic adenovirus Ad3-aLAG was stronger than that of Ad3 oncolytic adenovirus (P<0.01), and Ad3-aLAG could effectively enhance the infiltration of CD3+T cells in tumor tissue (P<0.01) and enhance the IFN- γ secretion ability of infiltrating T cells (P<0.01). Conclusion: Ad3-aLAG recombinant oncolytic adenovirus can significantly inhibit the growth of glioblastoma cells in vivo and in vitro, and enhance the anti-tumor immune response in vivo, which is promising to provide a new scheme for the treatment of glioblastoma.
2021, 28(1):17-22.
DOI: 10.3872/j.issn.1007-385X.2021.01.003
Abstract:
Objective: To explore the expression of long non-coding RNA (lncRNA) GTSE1-AS1 in prostate cancer tissues and the mechanism that affects the proliferation and invasion of LNCaP cells. Methods: From November 2017 to December 2018, 68 pairs of prostate cancer tissue and para-cancerous tissue specimens were resected from prostate cancer patients at the Department of Urology of Luoyang Central Hospital Affiliated to Zhengzhou University; in addition, prostate cancer cell lines LNCaP, PC-3, C4-2B, 22Rv1,DU-145 and normal prostate follicular epithelial RWPE-1 cells were also chosen for this study. qPCR was used to detect the expression level of GTSE1-AS1 in cancer tissues and cell lines. The GTSE1-AS1 over-expression plasmid (experimental group) and negative control plasmid (control group) were respectively transfected into LNCap cells. MTT assay and Transwell chamber method were used to detect the effect of GTSE1-AS1 over-expression on the proliferation and invasion ability of LNCaP cells, respectively. The targeting relationship among GTSE1-AS1 and miR-324-3P as well as FBXW7 (F-frame/WD repeat domain protein 7) was verified by bioinformatics tools and dual-luciferin reporter gene assay. The effect of GTSE1-AS1 over-expression on downstream gene and protein expression was detected by qPCR and WB assay. Results: The expression level of GTSE1-AS1 in prostate cancer tissues was significantly lower than that in para-cancerous tissues (P<0.01), and the expression of GTSE1-AS1 in prostate cancer cell lines was significantly lower than that in RWPE-1 cells (P<0.05 or P<0.01). Over-expression of GTSE1-AS1 significantly inhibited the proliferation and invasion (P<0.05 or P<0.01) of LNCaP cells. Dual-luciferin reporter gene assay confirmed the complementary binding between GTSE1-AS1 and miR-324-3p as well as between miR-324-3p and FBXW7. Over-expression of GTSE1-AS1 significantly reduced the expression of miR-324-3p in LNCaP cells (P<0.01), and promoted the mRNA and protein expressions of FBXW7 (all P<0.01). Conclusion: GTSE1-AS1 is under-expressed in prostate cancer tissues and cell lines. Over-expression of GTSE1-AS1 can inhibit the proliferation and invasion of LNCaP cells, the mechanism of which may be related with the inhibition of miR-324-3p to further promote FBXW7 expression.
Objective: To explore the expression of long non-coding RNA (lncRNA) GTSE1-AS1 in prostate cancer tissues and the mechanism that affects the proliferation and invasion of LNCaP cells. Methods: From November 2017 to December 2018, 68 pairs of prostate cancer tissue and para-cancerous tissue specimens were resected from prostate cancer patients at the Department of Urology of Luoyang Central Hospital Affiliated to Zhengzhou University; in addition, prostate cancer cell lines LNCaP, PC-3, C4-2B, 22Rv1,DU-145 and normal prostate follicular epithelial RWPE-1 cells were also chosen for this study. qPCR was used to detect the expression level of GTSE1-AS1 in cancer tissues and cell lines. The GTSE1-AS1 over-expression plasmid (experimental group) and negative control plasmid (control group) were respectively transfected into LNCap cells. MTT assay and Transwell chamber method were used to detect the effect of GTSE1-AS1 over-expression on the proliferation and invasion ability of LNCaP cells, respectively. The targeting relationship among GTSE1-AS1 and miR-324-3P as well as FBXW7 (F-frame/WD repeat domain protein 7) was verified by bioinformatics tools and dual-luciferin reporter gene assay. The effect of GTSE1-AS1 over-expression on downstream gene and protein expression was detected by qPCR and WB assay. Results: The expression level of GTSE1-AS1 in prostate cancer tissues was significantly lower than that in para-cancerous tissues (P<0.01), and the expression of GTSE1-AS1 in prostate cancer cell lines was significantly lower than that in RWPE-1 cells (P<0.05 or P<0.01). Over-expression of GTSE1-AS1 significantly inhibited the proliferation and invasion (P<0.05 or P<0.01) of LNCaP cells. Dual-luciferin reporter gene assay confirmed the complementary binding between GTSE1-AS1 and miR-324-3p as well as between miR-324-3p and FBXW7. Over-expression of GTSE1-AS1 significantly reduced the expression of miR-324-3p in LNCaP cells (P<0.01), and promoted the mRNA and protein expressions of FBXW7 (all P<0.01). Conclusion: GTSE1-AS1 is under-expressed in prostate cancer tissues and cell lines. Over-expression of GTSE1-AS1 can inhibit the proliferation and invasion of LNCaP cells, the mechanism of which may be related with the inhibition of miR-324-3p to further promote FBXW7 expression.
4 lncRNA GAS6-AS2 regulates paclitaxel sensitivity in lung cancer A549 cells by targeting miR-125a-3p
2021, 28(1):23-30.
DOI: 10.3872/j.issn.1007-385X.2021.01.004
Abstract:
Objective: To investigate the effects and molecular mechanism of lncRNA GAS6-AS2 on the proliferation, migration and invasion of lung cancer A549 cells and its sensitivity to paclitaxel (PTX). Methods: qPCR was used to detect the levels of GAS6-AS2 and miR-125a-3p in lung cancer A549 and A549/PTX cells. Si-NC, si-GAS6-AS2, miR-NC, miR-125A-3p, pcDNA,PCDNA-GAS6-AS2, si-GAS6-AS2+anti-miR-GAS6-AS2 and si-GAS6-AS2+anti-miR-125A-3p were transfected into A549/PTX cells by liposomal transfection.A549 and A549/PTX cells were treated with PTX of different concentrations (1 nmol/L, 5 nmol/L, 10 nmol/L,20 nmol/L, 40 nmol/L). WB was used to detect the expression levels of proliferation, migration and invasion related proteins (cyclin D1, p21, MMP2 and MMP9). MTT assay was used to determine the inhibitory effect of PTX on A549/PTX cell proliferation. Transwell assay was applied to detect cell migration and invasion ability of cells. Dual-luciferase reporter gene system was performed to verify the relationship between GAS6-AS2 and miR-125a-3p. Results: The expression level of GAS6-AS2 in A549/PTX cells was significantly higher than that in A549 cells (P<0.01), and the expression level of miR-125a-3p in A549/PTX cells was significantly lower than that in A549 cells (P<0.01). The inhibitory rates of PTX at different concentrations on A549/PTX cells were significantly lower than that on A549 cells (P<0.01), in a concentration-dependent manner. GAS6-AS2 knockdown or miR-125a-3p over-expression combined with PTX treatment could inhibit A549/PTX cell migration and invasion, enhance inhibition rate of PTX on cell proliferation, promote the expression of p21 protein, and suppress the expressions of cyclin D1, MMP2 and MMP9 (all P<0.01).GAS6-AS2 targeted and negatively regulated the expression of miR-125a-3p. Interfering miR-125a-3p reversed the effects of GAS6-AS2 knockdown on proliferation, migration, invasion and PTX sensitivity of A549/PTX cells (all P<0.01). Conclusion:GAS6-AS2 knockdown inhibits proliferation, migration and invasion of A549/PTX cells and enhances sensitivity of cells to PTX by targeting miR-125a-3p; thus, it can be used as a potential molecular target for lung cancer.
Objective: To investigate the effects and molecular mechanism of lncRNA GAS6-AS2 on the proliferation, migration and invasion of lung cancer A549 cells and its sensitivity to paclitaxel (PTX). Methods: qPCR was used to detect the levels of GAS6-AS2 and miR-125a-3p in lung cancer A549 and A549/PTX cells. Si-NC, si-GAS6-AS2, miR-NC, miR-125A-3p, pcDNA,PCDNA-GAS6-AS2, si-GAS6-AS2+anti-miR-GAS6-AS2 and si-GAS6-AS2+anti-miR-125A-3p were transfected into A549/PTX cells by liposomal transfection.A549 and A549/PTX cells were treated with PTX of different concentrations (1 nmol/L, 5 nmol/L, 10 nmol/L,20 nmol/L, 40 nmol/L). WB was used to detect the expression levels of proliferation, migration and invasion related proteins (cyclin D1, p21, MMP2 and MMP9). MTT assay was used to determine the inhibitory effect of PTX on A549/PTX cell proliferation. Transwell assay was applied to detect cell migration and invasion ability of cells. Dual-luciferase reporter gene system was performed to verify the relationship between GAS6-AS2 and miR-125a-3p. Results: The expression level of GAS6-AS2 in A549/PTX cells was significantly higher than that in A549 cells (P<0.01), and the expression level of miR-125a-3p in A549/PTX cells was significantly lower than that in A549 cells (P<0.01). The inhibitory rates of PTX at different concentrations on A549/PTX cells were significantly lower than that on A549 cells (P<0.01), in a concentration-dependent manner. GAS6-AS2 knockdown or miR-125a-3p over-expression combined with PTX treatment could inhibit A549/PTX cell migration and invasion, enhance inhibition rate of PTX on cell proliferation, promote the expression of p21 protein, and suppress the expressions of cyclin D1, MMP2 and MMP9 (all P<0.01).GAS6-AS2 targeted and negatively regulated the expression of miR-125a-3p. Interfering miR-125a-3p reversed the effects of GAS6-AS2 knockdown on proliferation, migration, invasion and PTX sensitivity of A549/PTX cells (all P<0.01). Conclusion:GAS6-AS2 knockdown inhibits proliferation, migration and invasion of A549/PTX cells and enhances sensitivity of cells to PTX by targeting miR-125a-3p; thus, it can be used as a potential molecular target for lung cancer.
2021, 28(1):31-36.
DOI: 10.3872/j.issn.1007-385X.2021.01.005
Abstract:
Objective: To investigate the effect of cytokeratin 13 (CK13) on radio-sensitivity of human nasopharyngeal carcinoma HNE1 cell line and its mechanism. Methods: HNE1 cells were divided into control group, anti-CK13#a group (CK13 knockdown),anti-CK13#b group (CK13 knockdown), control+sirolimus group (100 nmol/L sirolimus treatment for 1 h), and anti-CK13#a +sirolimus group (100 nmol/L sirolimus treatment for 1 h). After irradiation treatment (200 cGy/min irradiation for 5 min), cell proliferation in each group was measured by CCK-8 assay. Cell apoptosis rate in each group was determined by Flow cytometry.Expression of PI3K/AKT/mTOR signaling pathway related PTEN gene was detected by qPCR, and WB was used to detect the expressions of PI3K/AKT/mTOR signaling pathway related proteins. Results: In the case of radiotherapy, as compared with the control group, the proliferation of HNE1 cells after CK13 knockdown was significantly enhanced (P<0.01) while the apoptosis rate was significantly reduced (P<0.01), the contents of caspase-3 and γH2AX as well as the protein lever of PTEN in cells were significantly decreased, while the expressions of p-AKT and p-S6K were significantly increased (all P<0.01). Interestingly,additional treatment with sirolimus (PI3K/AKT/mTOR signaling pathway inhibitor) could rescue the accelerated cell proliferation and decreased cell apoptosis caused by CK13 knockdown (all P<0.05). Conclusion: CK13 knockdown can enhance the activity of PI3K/AKT/mTOR signaling pathway by down-regulating PTEN, and ultimately reduce the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells.
Objective: To investigate the effect of cytokeratin 13 (CK13) on radio-sensitivity of human nasopharyngeal carcinoma HNE1 cell line and its mechanism. Methods: HNE1 cells were divided into control group, anti-CK13#a group (CK13 knockdown),anti-CK13#b group (CK13 knockdown), control+sirolimus group (100 nmol/L sirolimus treatment for 1 h), and anti-CK13#a +sirolimus group (100 nmol/L sirolimus treatment for 1 h). After irradiation treatment (200 cGy/min irradiation for 5 min), cell proliferation in each group was measured by CCK-8 assay. Cell apoptosis rate in each group was determined by Flow cytometry.Expression of PI3K/AKT/mTOR signaling pathway related PTEN gene was detected by qPCR, and WB was used to detect the expressions of PI3K/AKT/mTOR signaling pathway related proteins. Results: In the case of radiotherapy, as compared with the control group, the proliferation of HNE1 cells after CK13 knockdown was significantly enhanced (P<0.01) while the apoptosis rate was significantly reduced (P<0.01), the contents of caspase-3 and γH2AX as well as the protein lever of PTEN in cells were significantly decreased, while the expressions of p-AKT and p-S6K were significantly increased (all P<0.01). Interestingly,additional treatment with sirolimus (PI3K/AKT/mTOR signaling pathway inhibitor) could rescue the accelerated cell proliferation and decreased cell apoptosis caused by CK13 knockdown (all P<0.05). Conclusion: CK13 knockdown can enhance the activity of PI3K/AKT/mTOR signaling pathway by down-regulating PTEN, and ultimately reduce the radio-sensitivity of nasopharyngeal carcinoma HNE1 cells.
2021, 28(1):37-42.
DOI: 10.3872/j.issn.1007-385X.2021.01.006
Abstract:
Objective: To investigate the expression of miR144-3p in bladder cancer tissues and cells and its effect on the proliferation and invasion of T24 cells. Methods: A total of 36 cases of bladder cancer tissue specimens and 10 cases of normal bladder epithelial tissue specimens were collected from Tangdu Hospital of Air Force Medical University during February 2018 and December 2018. In addition, bladder cancer T24 cell line and normal urothelial cell line SV-HUC-1 were also collected for this study. The levels of miR144-3p in bladder cancer tissues and cells were detected by qPCR methods. The miR-144-3p mimics and miR-NC were transfected into T24 cells by LipofectamineTM 2000, respectively. The proliferation, cell cycle distribution and invasion abilities were detected by MTT, Flow cytometry and Transwell chamber methods, respectively. TargetScan software was used to predict the binding site between miR-144-3p and E2F3 (E2F transcription factor 3); Dual luciferase reporter gene assay was used to verify the relationship between miR-144-3p and E2F3; and WB was used to detect the expression levels of miR-144-3p and E2F3 in cells. Results: The expression of miR-144-3p was downregulated in bladder cancer tissues and cells (all P<0.01). In addition, the expression level of miR-144-3p in muscular invasive bladder cancer tissues was significantly lower than that in non-muscular invasive bladder cancer tissues (P<0.05).Dual luciferase reporter gene assay confirmed that there was a targeted relationship between miR-144-3p and E2F3. Overexpression of miR-144-3p inhibited the proliferation and invasion of T24 cells (all P<0.01) and downregulated the expression of E2F3 (P<0.01);upregulation of E2F3 could reverse the inhibitory effect of miR-144-3p overexpression on proliferation and invasion of T24 cells.Conclusion: miR-144-3p has low expression level in bladder cancer tissues. It inhibits proliferation and invasion of bladder cancer cells by downregulating E2F3.
Objective: To investigate the expression of miR144-3p in bladder cancer tissues and cells and its effect on the proliferation and invasion of T24 cells. Methods: A total of 36 cases of bladder cancer tissue specimens and 10 cases of normal bladder epithelial tissue specimens were collected from Tangdu Hospital of Air Force Medical University during February 2018 and December 2018. In addition, bladder cancer T24 cell line and normal urothelial cell line SV-HUC-1 were also collected for this study. The levels of miR144-3p in bladder cancer tissues and cells were detected by qPCR methods. The miR-144-3p mimics and miR-NC were transfected into T24 cells by LipofectamineTM 2000, respectively. The proliferation, cell cycle distribution and invasion abilities were detected by MTT, Flow cytometry and Transwell chamber methods, respectively. TargetScan software was used to predict the binding site between miR-144-3p and E2F3 (E2F transcription factor 3); Dual luciferase reporter gene assay was used to verify the relationship between miR-144-3p and E2F3; and WB was used to detect the expression levels of miR-144-3p and E2F3 in cells. Results: The expression of miR-144-3p was downregulated in bladder cancer tissues and cells (all P<0.01). In addition, the expression level of miR-144-3p in muscular invasive bladder cancer tissues was significantly lower than that in non-muscular invasive bladder cancer tissues (P<0.05).Dual luciferase reporter gene assay confirmed that there was a targeted relationship between miR-144-3p and E2F3. Overexpression of miR-144-3p inhibited the proliferation and invasion of T24 cells (all P<0.01) and downregulated the expression of E2F3 (P<0.01);upregulation of E2F3 could reverse the inhibitory effect of miR-144-3p overexpression on proliferation and invasion of T24 cells.Conclusion: miR-144-3p has low expression level in bladder cancer tissues. It inhibits proliferation and invasion of bladder cancer cells by downregulating E2F3.
LI Yuan
,
FENG Jun
,
HUANG Hao
,
ZHU Yulan
,
ZHENG Panpan
,
XIAO Wenlu
,
CHEN Lujun
,
JIANG Jingting
,
LU Binfeng
2021, 28(1):43-47.
DOI: 10.3872/j.issn.1007-385X.2021.01.007
Abstract:
Objective: To investigate the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 (HHLA2) in hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological characteristics and prognosis of patients with HCC. Methods: Based on TCGA database, the correlation between HHLA2 mRNA expression and B7 family genes in human HCC tissues was analyzed. HHLA2 expression in 90 pairs of HCC tissues and their adjacent tissues was detected by tissue microarry and immunohistochemical staining. Wilcoxon rank sum test was used to compare the difference of HHLA2 expression between HCC tissues and its adjacent tissues. The chi-square test was used to analyze the relationship between HHLA2 expression in human HCC tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between HHLA2 expression and patients’overall survival (OS), and the Cox model was used to evaluate the prognostic value of different indices. Results: The expression level of HHLA2 mRNA in HCC tissues was correlated with B7 family CD274, C10orf54, PDCD1LG2, ICOSLG and CD276. The expression level of HHLA2 in HCC tissues was significantly correlated with tumor size (χ2=4.531, P<0.05). The OS of HCC patients with high HHLA2 expression was significantly shorter than that of the patients with lower HHLA2 expression (HR=1.878, 95%CI: 1.066-3.309, P<0.05). The COX model showed that tumor size (HR=2.493,95%CI: 1.310-4.742, P<0.01) could be used as an independent risk factor for the prognostic prediction of the patients. Conclusion:HHLA2 is significantly correlated with the prognosis of HCC patients, and can be used as a potential target for HCC immunotherapy.
Objective: To investigate the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 (HHLA2) in hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological characteristics and prognosis of patients with HCC. Methods: Based on TCGA database, the correlation between HHLA2 mRNA expression and B7 family genes in human HCC tissues was analyzed. HHLA2 expression in 90 pairs of HCC tissues and their adjacent tissues was detected by tissue microarry and immunohistochemical staining. Wilcoxon rank sum test was used to compare the difference of HHLA2 expression between HCC tissues and its adjacent tissues. The chi-square test was used to analyze the relationship between HHLA2 expression in human HCC tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between HHLA2 expression and patients’overall survival (OS), and the Cox model was used to evaluate the prognostic value of different indices. Results: The expression level of HHLA2 mRNA in HCC tissues was correlated with B7 family CD274, C10orf54, PDCD1LG2, ICOSLG and CD276. The expression level of HHLA2 in HCC tissues was significantly correlated with tumor size (χ2=4.531, P<0.05). The OS of HCC patients with high HHLA2 expression was significantly shorter than that of the patients with lower HHLA2 expression (HR=1.878, 95%CI: 1.066-3.309, P<0.05). The COX model showed that tumor size (HR=2.493,95%CI: 1.310-4.742, P<0.01) could be used as an independent risk factor for the prognostic prediction of the patients. Conclusion:HHLA2 is significantly correlated with the prognosis of HCC patients, and can be used as a potential target for HCC immunotherapy.
2021, 28(1):48-54.
DOI: 10.3872/j.issn.1007-385X.2021.01.008
Abstract:
Objective: To detect the expression of miR-126 in oral squamous cell carcinoma (OSCC) and to analyze its correlation with clinicopathological features and prognosis of patients, as well as to explore the effect of miR-126 over-expression on the malignant biological behaviors of Tca8113 cells. Methods: A total of 62 pairs of cancer and para-cancerous tissue specimens from OSCC patients who were surgically treated in the First Affiliated Hospital of Zhengzhou University from June 2016 to June 2018 were collected for this study; in addition, human tongue squamous carcinoma Tca8113 cell line and human mouth keratinocyte HOK cell line were also selected for this study. The expression of miR-126 in cancer tissues and cells was detected by qPCR, and the relationship between miR-126 expression and clinicopathological features and prognosis of the patients was analyzed. miR-126 mimics and miR-NC plasmids were respectively transfected into Tca8113 cells by liposome transfection technology. Cell proliferation, apoptosis, migration and invasion were detected by MTT method, Flow cytometry and Transwell chamber method, respectively; and the expressions of apoptosis, migration and invasion related proteins were detected by Western blotting. Results: The expression level of miR-126 in OSCC tissues and Tca8113 cells was significantly lower than that in para-cancerous tissues and HOK cells (all P<0.01). The expression of miR-126 was associated with TNM stage and lymph node metastasis (all P<0.05), and patients with high miR-126 expression had significantly better overall survival rate than patients with low expression (P<0.05). After transfection with miR-126 mimics, the cell proliferation, migration and invasion ability significantly decreased (P<0.05 or P<0.01) while the apoptosis rate significantly increased in Tca8113 cells (P<0.01), the expression levels of Bcl-2, N-cadherin and vimentin in Tca8113 cells significantly decreased (all P<0.01), and expression levels of Bax and E-cadherin significantly increased (all P<0.01). Conclusion: miR-126 is low expressed in OSCC tissues and Tca8113 cells. Up-regulation of miR-126 inhibits cell proliferation, migration and invasion and promotes apoptosis of Tca8113 cells.
Objective: To detect the expression of miR-126 in oral squamous cell carcinoma (OSCC) and to analyze its correlation with clinicopathological features and prognosis of patients, as well as to explore the effect of miR-126 over-expression on the malignant biological behaviors of Tca8113 cells. Methods: A total of 62 pairs of cancer and para-cancerous tissue specimens from OSCC patients who were surgically treated in the First Affiliated Hospital of Zhengzhou University from June 2016 to June 2018 were collected for this study; in addition, human tongue squamous carcinoma Tca8113 cell line and human mouth keratinocyte HOK cell line were also selected for this study. The expression of miR-126 in cancer tissues and cells was detected by qPCR, and the relationship between miR-126 expression and clinicopathological features and prognosis of the patients was analyzed. miR-126 mimics and miR-NC plasmids were respectively transfected into Tca8113 cells by liposome transfection technology. Cell proliferation, apoptosis, migration and invasion were detected by MTT method, Flow cytometry and Transwell chamber method, respectively; and the expressions of apoptosis, migration and invasion related proteins were detected by Western blotting. Results: The expression level of miR-126 in OSCC tissues and Tca8113 cells was significantly lower than that in para-cancerous tissues and HOK cells (all P<0.01). The expression of miR-126 was associated with TNM stage and lymph node metastasis (all P<0.05), and patients with high miR-126 expression had significantly better overall survival rate than patients with low expression (P<0.05). After transfection with miR-126 mimics, the cell proliferation, migration and invasion ability significantly decreased (P<0.05 or P<0.01) while the apoptosis rate significantly increased in Tca8113 cells (P<0.01), the expression levels of Bcl-2, N-cadherin and vimentin in Tca8113 cells significantly decreased (all P<0.01), and expression levels of Bax and E-cadherin significantly increased (all P<0.01). Conclusion: miR-126 is low expressed in OSCC tissues and Tca8113 cells. Up-regulation of miR-126 inhibits cell proliferation, migration and invasion and promotes apoptosis of Tca8113 cells.
2021, 28(1):55-59.
DOI: 10.3872/j.issn.1007-385X.2021.01.009
Abstract:
Objective: To investigate the expression of zinc-α2-glycoprotein 1 (AZGP1) in osteosarcoma tissue and its relationship with clinicopathological features and prognosis of patients. Methods: A total of 62 pairs of cancer tissue and adjacent normal tissue samples from patients with osteosarcoma treated in the Department of Orthopedics, Second People's Hospital of Nanyang City were collected from August 2012 to August 2014. The expressions of AZGP1 in osteosarcoma tissues and adjacent tissues were detected by using immunohistochemical staining. All patients were followed up on the second day after the operation. The deadline was August 31,2019. All patients were followed up for 5 years, with death as the end event. The number of end events within 5 years and overall survival (OS) time of the patients were recorded. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard model was used for multivariate analysis of factors affecting patients’survival. Results: The positive expression rate of AZGP1 in the osteosarcoma tissues was significantly higher than that in the adjacent tissues (77.42% vs 32.26%, P<0.01). There were significant differences in the positive expression rates of AZGP1 in patients with different Eneeking stages, soft tissue infiltration or not and lung metastasis conditions (all P<0.05). Kaplan-Meier survival analysis showed that the average OS time and 5-year OS rate of patients in the AZGP1 positive expression group were significantly lower than those in the negative expression group [(24.19±2.68) months vs (43.07±3.70) months, P<0.01; 18.75% vs 64.29%, P<0.01]. The lung metastasis and positive expression of AZGP1 were risk factors affecting the prognosis of patients with osteosarcoma (HR=3.407, 3.647, all P<0.05). Conclusion: AZGP1 is highly expressed in osteosarcoma tissues, and it is related to the malignant indicators and prognosis of patients. It may be a potential marker for evaluating the prognosis of osteosarcoma patients.
Objective: To investigate the expression of zinc-α2-glycoprotein 1 (AZGP1) in osteosarcoma tissue and its relationship with clinicopathological features and prognosis of patients. Methods: A total of 62 pairs of cancer tissue and adjacent normal tissue samples from patients with osteosarcoma treated in the Department of Orthopedics, Second People's Hospital of Nanyang City were collected from August 2012 to August 2014. The expressions of AZGP1 in osteosarcoma tissues and adjacent tissues were detected by using immunohistochemical staining. All patients were followed up on the second day after the operation. The deadline was August 31,2019. All patients were followed up for 5 years, with death as the end event. The number of end events within 5 years and overall survival (OS) time of the patients were recorded. Kaplan-Meier method was used for survival analysis, and Cox proportional hazard model was used for multivariate analysis of factors affecting patients’survival. Results: The positive expression rate of AZGP1 in the osteosarcoma tissues was significantly higher than that in the adjacent tissues (77.42% vs 32.26%, P<0.01). There were significant differences in the positive expression rates of AZGP1 in patients with different Eneeking stages, soft tissue infiltration or not and lung metastasis conditions (all P<0.05). Kaplan-Meier survival analysis showed that the average OS time and 5-year OS rate of patients in the AZGP1 positive expression group were significantly lower than those in the negative expression group [(24.19±2.68) months vs (43.07±3.70) months, P<0.01; 18.75% vs 64.29%, P<0.01]. The lung metastasis and positive expression of AZGP1 were risk factors affecting the prognosis of patients with osteosarcoma (HR=3.407, 3.647, all P<0.05). Conclusion: AZGP1 is highly expressed in osteosarcoma tissues, and it is related to the malignant indicators and prognosis of patients. It may be a potential marker for evaluating the prognosis of osteosarcoma patients.
2021, 28(1):60-66.
DOI: 10.3872/j.issn.1007-385X.2021.01.010
Abstract:
Objective: To investigate the expression of long non-coding RNA (lncRNA) HULC in bladder cancer tissues and its relationship with the clinicopathological features of patients, as well as the effect of silencing HULC on the proliferation, apoptosis,migration and invasion of bladder cancer 5637 cells. Methods: A total of 102 pairs of cancer tissue and adjacent normal tissue samples from bladder cancer patients who underwent surgical resection in Zhengzhou People’s Hospital from June 2014 to December 2017 were selected, as well as bladder cancer 5637 cell line and human normal bladder epithelial SV-HUC-1 cell line. The expression of HULC in bladder cancer tissues and cells was detected by qPCR, and the correlation between HULC and clinicopathological features of bladder cancer patients was analyzed. The effect of HULC on prognosis was evaluated by Kaplan-Meier survival curve. si-HUL and si-NC plasmids were transfected into 5637 cells by siRNA interference technology, and the effects of silencing HULC on proliferation, apoptosis, migration and invasion of 5637 cells were determined by CCK-8, Flow cytometry, Wound-healing assay and Transwell method, respectively. Results: The expression of HULC in bladder cancer tissues was significantly higher than that in normal tissues (P<0.05), and its expression level was correlated with tumor grade, tumor stage and lymph node metastasis (P<0.05).The OS and PFS of patients with high HULC expression were significantly lower than those with low expression (all P<0.05). The expression level of HULC in 5637 cells was significantly higher than that in SV-HUC-1 cells (P<0.01). After silencing HULC, the proliferation, migration and invasion of 5637 cells were significantly decreased (P<0.01), and the apoptosis rate was significantly increased (P<0.01). Conclusion: lncRNA HULC is highly expressed in bladder cancer tissues and 5637 cells. Silencing HULC expression can inhibit the proliferation, migration and invasion but promote apoptosis of bladder cancer cells.
Objective: To investigate the expression of long non-coding RNA (lncRNA) HULC in bladder cancer tissues and its relationship with the clinicopathological features of patients, as well as the effect of silencing HULC on the proliferation, apoptosis,migration and invasion of bladder cancer 5637 cells. Methods: A total of 102 pairs of cancer tissue and adjacent normal tissue samples from bladder cancer patients who underwent surgical resection in Zhengzhou People’s Hospital from June 2014 to December 2017 were selected, as well as bladder cancer 5637 cell line and human normal bladder epithelial SV-HUC-1 cell line. The expression of HULC in bladder cancer tissues and cells was detected by qPCR, and the correlation between HULC and clinicopathological features of bladder cancer patients was analyzed. The effect of HULC on prognosis was evaluated by Kaplan-Meier survival curve. si-HUL and si-NC plasmids were transfected into 5637 cells by siRNA interference technology, and the effects of silencing HULC on proliferation, apoptosis, migration and invasion of 5637 cells were determined by CCK-8, Flow cytometry, Wound-healing assay and Transwell method, respectively. Results: The expression of HULC in bladder cancer tissues was significantly higher than that in normal tissues (P<0.05), and its expression level was correlated with tumor grade, tumor stage and lymph node metastasis (P<0.05).The OS and PFS of patients with high HULC expression were significantly lower than those with low expression (all P<0.05). The expression level of HULC in 5637 cells was significantly higher than that in SV-HUC-1 cells (P<0.01). After silencing HULC, the proliferation, migration and invasion of 5637 cells were significantly decreased (P<0.01), and the apoptosis rate was significantly increased (P<0.01). Conclusion: lncRNA HULC is highly expressed in bladder cancer tissues and 5637 cells. Silencing HULC expression can inhibit the proliferation, migration and invasion but promote apoptosis of bladder cancer cells.
2021, 28(1):67-73.
DOI: 10.3872/j.issn.1007-385X.2021.01.011
Abstract:
Objective: To investigate the expression of transgelin (TAGLN) in colorectal cancer (CRC) tissues and its effect on the proliferation, migration and invasion of CRC SW480 cells. Methods: Surgically resected CRC tissues and corresponding paracancerous tissues of 97 CRC patients from May 2015 to August 2016 in the Affiliated Tumor Hospital of Zhengzhou University were collected; In addition, CRC cell lines SW620, SW480, HCT116 and normal colorectal mucosal cell line FHC were also collected for this study. Immunohistochemical staining was used to detect the expression of TAGLN in CRC tissues, and the correlation between TAGLN and patients’clinicopathological features was analyzed. Quantitative Real-time quantitative polymerase chain reaction (qPCR)and Western blotting (WB) were used to detect the mRNA and protein expressions of TAGLN in CRC cell lines. si-TAGLN and si-Ctrl were respectively transfected into SW480 cells by liposome transfection method. The effects of silencing TAGLN on the proliferation, migration and invasion of SW480 cells were detected by CCK-8, Wound-healing assay and Transwell assay,respectively; and the expression of EMT-related proteins E-cadherin, N-cadherin and vimentin were detected by WB. Results: The positive expression rate of TAGLN in CRC tissues was significantly higher than that in para-cancerous tissues (P<0.01), and TAGLN expression was correlated with TNM stage, degree of tumor differentiation and lymph node metastasis in CRC patients (P<0.05 or P<0.01). The mRNA and protein expression levels of TAGLN in SW480 cells were significantly higher than those in FHC cells (all P<0.01). After TAGLN silence, the proliferation, invasion and migration ability of SW480 cells were significantly reduced (all P<0.01), the expression level of E-cadherin in SW480 cells was increased, while the expression levels of N-cadherin and vimentin were decreased (all P<0.01). Conclusion: TAGLN is highly expressed in CRC tissues and cells. Silencing TAGLN can inhibit the proliferation, invasion and migration of CRC cells, suggesting that TAGLN plays an important role in the occurrence and development of CRC.
Objective: To investigate the expression of transgelin (TAGLN) in colorectal cancer (CRC) tissues and its effect on the proliferation, migration and invasion of CRC SW480 cells. Methods: Surgically resected CRC tissues and corresponding paracancerous tissues of 97 CRC patients from May 2015 to August 2016 in the Affiliated Tumor Hospital of Zhengzhou University were collected; In addition, CRC cell lines SW620, SW480, HCT116 and normal colorectal mucosal cell line FHC were also collected for this study. Immunohistochemical staining was used to detect the expression of TAGLN in CRC tissues, and the correlation between TAGLN and patients’clinicopathological features was analyzed. Quantitative Real-time quantitative polymerase chain reaction (qPCR)and Western blotting (WB) were used to detect the mRNA and protein expressions of TAGLN in CRC cell lines. si-TAGLN and si-Ctrl were respectively transfected into SW480 cells by liposome transfection method. The effects of silencing TAGLN on the proliferation, migration and invasion of SW480 cells were detected by CCK-8, Wound-healing assay and Transwell assay,respectively; and the expression of EMT-related proteins E-cadherin, N-cadherin and vimentin were detected by WB. Results: The positive expression rate of TAGLN in CRC tissues was significantly higher than that in para-cancerous tissues (P<0.01), and TAGLN expression was correlated with TNM stage, degree of tumor differentiation and lymph node metastasis in CRC patients (P<0.05 or P<0.01). The mRNA and protein expression levels of TAGLN in SW480 cells were significantly higher than those in FHC cells (all P<0.01). After TAGLN silence, the proliferation, invasion and migration ability of SW480 cells were significantly reduced (all P<0.01), the expression level of E-cadherin in SW480 cells was increased, while the expression levels of N-cadherin and vimentin were decreased (all P<0.01). Conclusion: TAGLN is highly expressed in CRC tissues and cells. Silencing TAGLN can inhibit the proliferation, invasion and migration of CRC cells, suggesting that TAGLN plays an important role in the occurrence and development of CRC.
2021, 28(1):74-81.
DOI: 10.3872/j.issn.1007-385X.2021.01.012
Abstract:
肝细胞癌（hepatocellular carcinoma，HCC）是世界范围内最常见的原发性肝恶性肿瘤。当HCC患者出现明显症状时，肿瘤往往已经是中晚期，极大地影响了患者的生存质量。肝癌祖细胞（hepatocellular carcinoma progenitor cell，HcPC）是一种癌前病变中所含有的肿瘤起始细胞，对HcPC的发生机制以及生物学功能进行系统阐述，可能对HCC的早期诊断和干预治疗具有潜在的重要意义。近年来已有大量文献报道HcPC的生物标志物，如CD44、EpCAM、SOX9、OV6以及CK19等在HCC发生中所发挥重要作用，它们表达水平的升高对肝细胞的恶性转化、HcPC干性的维持以及肿瘤细胞的迁移和侵袭均具有一定的促进作用。针对HcPC的研究有望为HCC早期诊断提供新的思路，而通过阻止HcPC向HCC的恶性转化也有望成为一种治疗HCC的新方法。本文尝试对 HcPC 的发现过程、HcPC 的主要来源、现有 HcPC 相关生物标志物等进行较为系统的综述，期望有助于今后HcPC相关研究的深入开展。
肝细胞癌（hepatocellular carcinoma，HCC）是世界范围内最常见的原发性肝恶性肿瘤。当HCC患者出现明显症状时，肿瘤往往已经是中晚期，极大地影响了患者的生存质量。肝癌祖细胞（hepatocellular carcinoma progenitor cell，HcPC）是一种癌前病变中所含有的肿瘤起始细胞，对HcPC的发生机制以及生物学功能进行系统阐述，可能对HCC的早期诊断和干预治疗具有潜在的重要意义。近年来已有大量文献报道HcPC的生物标志物，如CD44、EpCAM、SOX9、OV6以及CK19等在HCC发生中所发挥重要作用，它们表达水平的升高对肝细胞的恶性转化、HcPC干性的维持以及肿瘤细胞的迁移和侵袭均具有一定的促进作用。针对HcPC的研究有望为HCC早期诊断提供新的思路，而通过阻止HcPC向HCC的恶性转化也有望成为一种治疗HCC的新方法。本文尝试对 HcPC 的发现过程、HcPC 的主要来源、现有 HcPC 相关生物标志物等进行较为系统的综述，期望有助于今后HcPC相关研究的深入开展。
2021, 28(1):82-89.
DOI: 10.3872/j.issn.1007-385X.2021.01.013
Abstract:
人类肠道菌群种类超过1 000种，是人体内最庞大的微生物群，被称为“被遗忘的器官”。肠道菌群易受多种因素影响。已有多项研究证明肠道菌群及其代谢产物参与宿主免疫构建和影响肿瘤微环境，与肿瘤对免疫检查点抑制剂（immune checkpoint inhibitor，ICI）的应答和ICI治疗相关不良反应的发生有关。随着人类微生物组计划的开展和测序分析技术的进步，肠道菌群的相关研究逐步深入，基因功能注释和代谢组学分析的成熟和推广丰富了肠道菌群与宿主免疫及免疫治疗间的探索维度，干预和塑造肠道菌群为提高肿瘤免疫治疗效果提供了新的思路。然而，微生物制品的食源性添加、粪菌移植等研究尚未获得足够证据，肠道菌群的免疫调控机制尚不完全清楚。本文就近年来肠道菌群影响肿瘤对ICI应答机制的研究进展作一综述。
人类肠道菌群种类超过1 000种，是人体内最庞大的微生物群，被称为“被遗忘的器官”。肠道菌群易受多种因素影响。已有多项研究证明肠道菌群及其代谢产物参与宿主免疫构建和影响肿瘤微环境，与肿瘤对免疫检查点抑制剂（immune checkpoint inhibitor，ICI）的应答和ICI治疗相关不良反应的发生有关。随着人类微生物组计划的开展和测序分析技术的进步，肠道菌群的相关研究逐步深入，基因功能注释和代谢组学分析的成熟和推广丰富了肠道菌群与宿主免疫及免疫治疗间的探索维度，干预和塑造肠道菌群为提高肿瘤免疫治疗效果提供了新的思路。然而，微生物制品的食源性添加、粪菌移植等研究尚未获得足够证据，肠道菌群的免疫调控机制尚不完全清楚。本文就近年来肠道菌群影响肿瘤对ICI应答机制的研究进展作一综述。
2021, 28(1):90-96.
DOI: 10.3872/j.issn.1007-385X.2021.01.014
Abstract:
人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）阳性胃癌是胃癌的重要亚型，靶向HER2的免疫治疗能显著改善晚期胃癌患者的预后，并已成为晚期胃癌的一线标准治疗。免疫治疗是肿瘤治疗领域的研究热点，通过直接或间接地调动机体的固有和适应性免疫发挥抗肿瘤效应。免疫治疗在晚期胃癌中的应用主要集中在二线、三线及以后，其在HER2阳性胃癌患者中的小样本试验性应用获得了初步的疗效，提示HER2阳性胃癌免疫治疗的使用具有进一步研究的价值。本文将从现有的主要免疫治疗手段——免疫检查点抑制剂、嵌合抗原受体T细胞（chimeric antigen receptor T-cell，CAR-T细胞）和治疗性疫苗三个方面，整合临床前实验与相关临床试验的数据，阐述HER2阳性胃癌免疫治疗的研究进展，探讨HER2阳性胃癌免疫治疗的潜在机制，同时对免疫治疗的疗效与安全性进行综合评价，展望HER2阳性胃癌免疫治疗的广阔前景及研究的新方向。
人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）阳性胃癌是胃癌的重要亚型，靶向HER2的免疫治疗能显著改善晚期胃癌患者的预后，并已成为晚期胃癌的一线标准治疗。免疫治疗是肿瘤治疗领域的研究热点，通过直接或间接地调动机体的固有和适应性免疫发挥抗肿瘤效应。免疫治疗在晚期胃癌中的应用主要集中在二线、三线及以后，其在HER2阳性胃癌患者中的小样本试验性应用获得了初步的疗效，提示HER2阳性胃癌免疫治疗的使用具有进一步研究的价值。本文将从现有的主要免疫治疗手段——免疫检查点抑制剂、嵌合抗原受体T细胞（chimeric antigen receptor T-cell，CAR-T细胞）和治疗性疫苗三个方面，整合临床前实验与相关临床试验的数据，阐述HER2阳性胃癌免疫治疗的研究进展，探讨HER2阳性胃癌免疫治疗的潜在机制，同时对免疫治疗的疗效与安全性进行综合评价，展望HER2阳性胃癌免疫治疗的广阔前景及研究的新方向。
2021, 28(1):97-101.
DOI: 10.3872/j.issn.1007-385X.2021.01.015
Abstract:
胃癌是世界范围内第五大常见恶性肿瘤，居肿瘤相关死亡原因的第三位。晚期诊断、高复发和高转移与其不良预后相关。胃癌的发病机制非常复杂，其潜在机制尚待探索。环状RNA（circular RNA，circRNA）是一类以单链共价闭环结构为特征的新型长链非编码RNA，主要在转录和转录后水平上参与基因表达调控。近年来研究发现，circRNA参与许多生物学过程，包括肿瘤的发生和发展。circRNA在胃癌中起着关键作用，其在胃癌中异常表达与胃癌组织的病理特征相关，并通过调控一些靶基因、miRNA和蛋白质的表达，参与调控胃癌细胞的增殖、迁移、侵袭和凋亡等生物学过程，提示circRNA可能是胃癌诊断和预后潜在的生物标志物和治疗靶点。本文论述近年来circRNA的生物学功能及其在胃癌诊治中作用的相关研究进展。
胃癌是世界范围内第五大常见恶性肿瘤，居肿瘤相关死亡原因的第三位。晚期诊断、高复发和高转移与其不良预后相关。胃癌的发病机制非常复杂，其潜在机制尚待探索。环状RNA（circular RNA，circRNA）是一类以单链共价闭环结构为特征的新型长链非编码RNA，主要在转录和转录后水平上参与基因表达调控。近年来研究发现，circRNA参与许多生物学过程，包括肿瘤的发生和发展。circRNA在胃癌中起着关键作用，其在胃癌中异常表达与胃癌组织的病理特征相关，并通过调控一些靶基因、miRNA和蛋白质的表达，参与调控胃癌细胞的增殖、迁移、侵袭和凋亡等生物学过程，提示circRNA可能是胃癌诊断和预后潜在的生物标志物和治疗靶点。本文论述近年来circRNA的生物学功能及其在胃癌诊治中作用的相关研究进展。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.