[摘 要] 目的：探究DNA聚合酶δ催化亚基1（POLD1）在膀胱癌组织中的表达，并探讨其与患者临床病理特征及预后的关系； POLD1对膀胱癌5637细胞增殖、迁移和侵袭的影响。方法：收集2021年1月至2021年6月在山西白求恩医院病理科保存的 60例膀胱癌组织及相应的癌旁组织，免疫组化法检测POLD1蛋白在膀胱癌组织中的表达，根据POLD1表达水平将患者分为高 表达和低表达组，分析其表达水平与患者临床特征及预后的关系。常规培养5637细胞，随机分为对照组（不转染）、sh-NC组（转 染sh-NC-GFP慢病毒载体）和sh-POLD1组（转染sh-POLD1-GFP慢病毒载体）。荧光显微镜和WB法验证其转染效率。CCK-8 法、划痕愈合实验和Transwell实验分别检测各组细胞的增殖、迁移和侵袭能力。5637细胞移植瘤实验检测敲减POLD1对移植瘤 生长的影响。结果：膀胱癌组织中POLD1呈高表达（P < 0.05），POLD1高表达与临床分期和病理分级均有明显关联（均 P < 0.05），POLD1高表达患者的无进展生存期、总生存期和3年生存率均明显缩短或降低（均P < 0.05），复发率和转移率均 更高（均P < 0.05）。在5637细胞中成功地敲减了POLD1的表达，敲减POLD1表达能明显抑制5637细胞的增殖、迁移和侵袭能力 （均P < 0.05）。敲减POLD1能明显抑制移植瘤的生长（P < 0.05）。结论： POLD1在膀胱癌组织中呈高表达，其高表达与肿瘤临 床分期、病理分级和患者预后有关联，敲减其表达可抑制膀胱癌细胞的恶性生物学行为。

[Abstract] Objective: To investigate the expression of DNA polymerase δ catalytic subunit gene 1 (POLD1) in bladder cancer tissues and its correlation with patients’ clinicopathological characteristics and prognosis, and to explore its effect on the proliferation, migration, and invasion of bladder cancer 5637 cells. Methods: Sixty cases of bladder cancer tissues and paired adjacent noncancerous tissues preserved in the Department of Pathology, Shanxi Bethune Hospital, from January to June 2021 were collected. Immunohistochemistry was performed to detect POLD1 protein expression in bladder cancer tissues. Patients were divided into high- and low-expression groups according to POLD1 levels, and the correlations between POLD1 level with clinicopathological characteristics and prognosis were analyzed. Bladder cancer 5637 cells were cultured routinely and divided into a control group (untransfected), a sh-NC group (transfected with sh-NC-GFP lentivirus vector), and a sh-POLD1 group (transfected with sh-POLD1 GFP lentiviral vector). Transfection efficiency was validated using fluorescence microscopy and WB method. Cell proliferation, migration, and invasion were assessed using CCK-8, wound-healing, and Transwell assays. 5637 cell-transplanted tumor experiment was performed to detect the effect of POLD1 knockdown on the growth of transplanted tumors. Results: POLD1 was highly expressed in bladder cancer tissues (P < 0.05). High POLD1 expression was significantly associated with advanced clinical stage and pathological grade (all P < 0.05). Patients with high POLD1 expression exhibited shorter progression-free survival, reduced overall survival, lower 3 year survival rate, and higher recurrence and metastasis rate (all P < 0.05). The expression of POLD1 was successfully knocked down in 5637 cells, which significantly inhibited the proliferation, migration, and invasion abilities of 5637 cells (all P < 0.05). In vivo, POLD1 knockdown significantly inhibited the growth of transplanted tumors (P < 0.05). Conclusion: POLD1 is highly expressed in bladder cancer tissues, and its upregulation is associated with tumor stage, pathological grade, and patient prognosis. POLD1 knockdown can inhibit the malignant biological behaviors of bladder cancer cells.

[基金项目] 山西省基础研究计划（No.202203021221242）