胰腺癌中CLDN-7的表达及临床意义

目的： 探讨紧密连接蛋白claudin-7 （CLDN-7）在胰腺癌中的表达情况，以及其与患者临床病理特征和预后的相关性。方法： 应用Oncomine、GEPIA和GEO数据库综合分析CLDN-7 mRNA在胰腺癌中的表达水平，应用Kaplan-Meier Plotter数据库分析胰腺癌中CLDN-7的表达水平与生存预后的关系；选取兰州大学第二医院普外科2015年至2018年手术切除的44例胰腺癌患者的癌组织及31例癌旁组织标本，采用免疫组织化学染色法检测CLDN-7蛋白的表达水平，并分析其与临床病理特征以及预后的关系；GO分析和KEGG通路富集分析 CLDN-7可能参与的信号通路及发挥的主要功能，并且在TCGA和GEPIA数据库中进行验证。 结果： 数据库及收取的临床样本分析均显示，CLDN-7在胰腺癌组织中显著高表达, 其高表达与胰腺癌患者临床预后有关联，并且CLDN-7的表达水平是影响胰腺癌患者术后总体生存时间的独立因素（均P<0.05）；GO分析和KEGG通路富集分析证实，CLDN-7参与胰腺癌患者DNA损伤修复、糖代谢等；TCGA和GEPIA数据库验证显示，胰腺癌中CLDN-7的表达与DNA损伤修复相关基因POLD4、SMUG1、NTHL1 及糖代谢的相关基因 ALDOA、TALDO1、PGLS 的表达呈现出明显的正相关性（均P<0.01）。 结论： CLDN-7在胰腺癌中高表达且标志着更差的临床预后，并与胰腺癌的DNA损伤修复及肿瘤内糖代谢相关。

Expression and clinical significance of CLDN-7 in pancreatic cancer

Objective: To investigate the expression of tight junction protein claudin-7 (CLDN-7) in pancreatic cancer and its correlation with the clinicopathological features and prognosis of pancreatic cancer patients. Methods: Oncomine, GEPIA and GEO databases were used to comprehensively analyze the mRNA expression level of CLDN-7 in pancreatic cancer, and Kaplan-Meier Plotter database was used to analyze the relationship between the expression of CLDN-7 and the survival prognosis of pancreatic cancer patients. Immunohistochemical staining was used to detect the protein level of CLDN-7 in 44 cases of pancreatic cancer tissues and 31 cases of para-cancerous tissues resected in the Department of General Surgery of the Second Hospital of Lanzhou University from 2015 to 2018, and the relationship between CLDN-7 expression and clinicopathological characteristics and prognosis of patients was also analyzed. GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis were conducted to analyze the possible signaling pathways that CLDN-7 may involve in and their main functions, which were further verified in TCGA and GEPIA databases. Results: Analysis of both the databases and the clinical samples showed that CLDN-7 was significantly over-expressed in pancreatic cancer tissues, and its high expression was correlated with clinical prognosis of pancreatic cancer patients; moreover, CLDN-7 expression was an independent factor affecting the overall survival time of pancreatic cancer patients (all P<0.05). GO analysis and KEGG pathway enrichment analysis confirmed that CLDN-7 was involved in DNA damage repair and glucose metabolism in pancreatic cancer patients. TCGA and GEPIA database validation showed that CLDN-7 expression in pancreatic cancer was significantly and positively correlated with the expression of DNA damage repair related genes (POLD4, SMUG1, NTHL1) and glucose metabolism related genes (ALDOA, TALDO1, PGLS) (all P<0.01). Conclusion: CLDN-7 is highly expressed in pancreatic cancer and indicates a worse clinical prognosis; moreover, CLDN-7 is associated with DNA damage repair and intratumoral glucose metabolism in pancreatic cancer.