[摘 要] 目的：探究钾钙激活通道亚家族N成员4（KCNN4）在胰腺癌组织中的表达及其对胰腺癌进展的影响，解析KCNN4 在胰腺癌临床诊断及预后判断中的作用。方法：利用GEPIA2数据分析平台，结合TCGA和GTEx数据库的数据分析KCNN4在 胰腺癌组织中的表达水平及其与患者预后的关系。收集24例海军军医大学长海医院手术切除的胰腺癌患者的癌及癌旁组织标 本，通过qPCR、WB法和免疫组化染色技术验证KCNN4在胰腺癌组织中的表达水平。利用shRNA敲低人胰腺癌细胞中BXPC3 和PANC-1中KCNN4的表达，通过CCK-8和克隆形成实验检测细胞增殖与生长情况。利用小鼠胰腺癌KPC细胞构建胰腺癌原 位成瘤模型，观察敲低KCNN4对胰腺原位成瘤的影响，统计小鼠生存期（OS）。结果：整合TCGA和GTEx数据库数据分析结果 发现，KCNN4在胰腺癌组织中高表达（P < 0.05），且与患者OS和DFS缩短相关（均P < 0.05）。胰腺癌组织中KCNN4 mRNA和蛋 白表达量均显著高于癌旁组织（均P < 0.01）。KCNN4敲低后，胰腺癌细胞生长速率显著减慢、克隆形成数量显著减少（均P < 0.01）。 小鼠胰腺原位荷瘤实验结果表明，KCNN4敲低可抑制肿瘤细胞在胰腺原位的生长并延长小鼠OS。结论：KCNN4在胰腺癌组织 中高表达，其能促进胰腺癌细胞增殖和胰腺癌进展，与患者预后密切相关，有望作为胰腺癌临床诊断及预后评估的靶点。

[Abstract] Objective: To investigate the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) in pancreatic cancer tissues and its impact on tumor progression, and to explore its role in clinical diagnosis and prognosis evaluation of pancreatic cancer. Methods: Using the GEPIA2 data analysis platform, the expression of KCNN4 in pancreatic cancer tissues and its correlation with patient prognosis were analyzed by integrating data from the TCGA and GTEx databases. Cancerous and adjacent non cancerous tissues from 24 patients with pancreatic cancer who underwent surgical resection at ChangHai Hospital of the Naval Medical University were collected. The expression of KCNN4 in pancreatic cancer tissues was validated using qPCR, Western blotting, and immunohistochemical staining. The expression of KCNN4 in human pancreatic cancer cell lines BXPC3 and PANC-1 was knocked down using shRNA. CCK-8 and colony formation assays were performed to detect tumor cell proliferation and growth. A murine KPC cell pancreatic cancer model was established to investigate the effects of KCNN4 knockdown on the growth of orthotopic pancreatic tumor and overall survival (OS) in mice. Results: Analysis of TCGA and GTEx data revealed that KCNN4 was highly expressed in pancreatic cancer tissues (P < 0.05) and was associated with shortened OS and disease-free survival (DFS) in patients (both P < 0.05). The expression levels of KCNN4 mRNA and protein were significantly elevated in pancreatic cancer tissues compared with those in adjacent non-cancerous tissues (all P < 0.01). Knockdown of KCNN4 led to significantly reduced growth rates and fewer colony formations in pancreatic cancer cells (both P < 0.01). The murine orthotopic pancreatic tumor experiment revealed that KCNN4 knockdown inhibited tumor progression and prolonged the OS of mice. Conclusion: KCNN4, highly expressed in pancreatic cancer tissues, promotes pancreatic cancer cell proliferation and tumor progression, and its expression is closely associated with patient prognosis, suggesting that KCNN4 may serve as a promising target for clinical diagnosis and prognosis evaluation of pancreatic cancer.

国家自然科学基金（No. 32170918）