染色体结构维持蛋白4在胰腺癌中表达的临床与生物信息学分析

The expression and bioinformatics analysis of structural maintenance of chromosome 4 in pancreatic cancer

目的 研究染色体结构维持蛋白4(structural maintenance of chromosome 4,SMC4)在胰腺癌组织中的表达差异及其与临床病理特征和预后的关系,并探讨其可能发生相互作用的蛋白网络及调控的可能信号通路。方法 采用Western blotting检测中国人民解放军中部战区总医院收集的12例胰腺癌组织及癌旁组织中SMC4蛋白表达,比较表达的差异。比较GEPIA数据库中SMC4在胰腺癌组织及正常胰腺组织中的mRNA表达差异。采用Cox回归、Kaplan-Meier法分析TCGA数据库中SMC4基因表达差异与胰腺癌患者临床病理特征和预后的关系。通过STRING数据库分析与SMC4相互作用的蛋白网络。采用GSEA预测TCGA数据库中SMC4在胰腺癌中调控的可能信号通路。结果 SMC4的临床表达:(1)对我院的12例样本Western blotting检测显示SMC4在胰腺癌组织中的蛋白表达量高于癌旁组织;(2)GEPIA数据库分析显示SMC4在胰腺癌组织中的mRNA表达量高于正常胰腺组织;(3)TCGA数据库分析结果显示SMC4基因表达水平与胰腺癌患者的病理分级和T分期密切相关。Cox分析结果显示,SMC4 mRNA表达水平和N分期是胰腺癌患者预后的独立危险因素。SMC4高表达组胰腺癌患者的生存时间显著低于SMC4低表达组患者。生物信息学分析结果:(1)STRING数据库分析表明与SMC4相互作用蛋白有NCAPH、NCAPG、SMC2等;(2)GSEA研究显示,SMC4 mRNA高表达样本富集到ERBB信号通路、WNT信号通路、TGF-β信号通路等相关基因集。结论 SMC4在胰腺癌中高表达,且与胰腺癌不良预后密切相关,可能通过调节SMC2等相互作用蛋白及激活TGF-β等信号通路在胰腺癌发生发展中发挥促癌作用。

objective To investigate the expression of structural maintenance of chromosome 4(SMC4) in pancreatic cancer and its association with clinicopathological features and prognosis, and to predict the protein network of the interactions and the possible signal pathways of SMC4 in pancreatic cancer. Methods Western blotting was used to detect the protein expression of SMC4 in 12 cases of pancreatic cancer tissues and adjacent normal tissues collected from General Hospital of Central Theater Command of PLA. Meanwhile, the mRNA expression of SMC4 in pancreatic cancer tissues and normal pancreatic tissues in GEPIA database were compared and analyzed. Cox regression analysis and Kaplan-Meier method were used to analyze the correlation between expression level of SMC4 and clinicopathological features and prognosis of pancreatic cancer patients in TCGA database. The STRING database was used to analyze the network of proteins interacting with SMC4. GSEA was employed to predict the possible signal pathways of SMC4 in pancreatic cancer. Results Expression of SMC4 in pancreatic cancer:(1) Western blotting results showed that SMC4 protein expression in pancreatic cancer tissues was higher than that in in normal pancreatic tissues.(2) GEPIA results showed that SMC4 mRNA expression in pancreatic cancer tissues was higher than that in adjacent normal tissues.(3) Analysis about TCGA database showed that SMC4 gene expression level was associated with pathological grade and T stage. Results of Cox analysis showed that SMC4 mRNA expression level and N stage were independent factors affecting overall survival of pancreatic cancer patients. Compared with the SMC4 low expression group, the survival time of pancreatic cancer patients in SMC4 high expression group was shorter.(1) STRING database showed that there was an interaction between SMC4 and NCAPH, NCAPG, SMC2 and so on.(2) GSEA research results showed that the SMC4 mRNA high expression samples were enriched into ERBB signaling pathway, WNT signaling pathway, TGF-β signaling pathway and so on. Conclusion SMC4 is highly expressed in pancreatic cancer tissues, and is closely associated with poor prognosis of HCC. Moreover, it may promote progress of pancreatic cancer by regulating interacting proteins such as SMC2 and activating signaling pathways such as TGF-β.