表皮生长因子受体与乳酸脱氢酶在胰腺癌中的表达及意义的TIMER数据库分析

TIMER database analysis of expressions and significance of epidermal growth factor receptor and lactate dehydrogenase in pancreatic cancer

目的:应用生物信息学方法探讨表皮生长因子受体(EGFR)及乳酸脱氢酶(LDHA)在胰腺癌局部免疫微环境中的表达及意义。方法:运行TIMER(Tumor IMmune Estimation Resource)数据库,获取178例胰腺癌患者的临床信息,以及患者组织标本中EGFR、LDHA、胰腺癌相关信号分子的表达以及各亚群免疫细胞浸润数据,通过人类蛋白表达图谱,搜索EGFR、LDHA以及胰腺癌相关信号分子的蛋白表达丰度。采用Log-rank检验及Cox比例风险回归模型分析EGFR与LDHA表达以及各亚群免疫细胞与其他临床因素对患者预后的影响,并分析EGFR与LDHA与两者与胰腺癌相关信号分子的关系。结果:胰腺癌组织中EGFR与LDHA mRNA的表达水平均明显高于正常胰腺组织(均P<0.05);在胰腺癌组织中,EGFR和LDHA mRNA呈正相关(P<0.001)。EGFR mRNA高表达、LDHA mRNA高表达、低水平CD4^+T细胞的胰腺癌患者总体生存率较差(均P<0.05)。LDHA是胰腺癌的独立预后因素(P<0.001)。EGFR与胰腺癌相关信号分子P38、FOXM1、PD-L1、CSF1、CSF1R表达呈明显正相关,而LDHA与FOXM1、CSF1、CSF1R表达呈明显正相关(均P<0.001)。EGFR、LDHA、P38、FOXM1和CSF1R蛋白在胰腺癌组织的表达丰度高于正常胰腺组织。结论:在胰腺癌组织中,EGFR与LDHA的表达升高,两者尤其是LDHA,可能通过对胰腺癌相关信号分子表达及局部免疫微环境的调控,从而影响患者预后。

Objective: To investigate the expressions of epidermal growth factor receptor(EGFR) and lactate dehydrogenase(LDHA) in the local immune microenvironment of pancreatic cancer and significance by bioinformatics approaches.Methods: The clinical information of 178 pancreatic cancer patients along with the expression data of EGFR, LDHA and signaling molecules associated with pancreatic cancer as well as the infiltration levels of distinct immune cell subsets in their tissue samples were retrieved by mining the TIMER(Tumor IMmune Estimation Resource) web server, and the protein expression abundances of EGFR and LDHA together with the signaling molecules associated with pancreatic cancer were examined by using the Human Protein Atlas. The influences of EGFR and LDHA expressions as well as the infiltration levels of immune cell subsets and other clinical factors on prognosis of the patients were analyzed by Log-rank test and Cox regression model, and the relationship between EGFR and LDHA and their relations with the signaling molecules associated with pancreatic cancer were also analyzed.Results: The mRNA expression levels of both EGFR and LDHA in pancreatic cancer tissue were significantly higher than those in normal pancreatic tissue(both P<0.05); there was a positive correlation between EGFR and LDHA mRNA expressions in pancreatic cancer tissue(P<0.001). High EGFR mRNA expression, high LDHA mRNA expression and low level of CD4^+ T cells were significantly associated with poor overall survival in pancreatic cancer patients(all P<0.05). LDHA was an independent prognostic factor for pancreatic cancer(P<0.001). EGFR was positively correlated with the expressions of the signaling molecules associated with pancreatic cancer that included FOXM1, CSF1 and CSF1 R mRNA, and LDHA was positively correlated with the expressions of FOXM1, CSF1 and CSF1 R(all P<0.05). The protein expression abundances of EGFR, LDHA, P38, FOXM1 and CSF1 R in pancreatic cancer tissue were all markedly higher than those in normal pancreatic tissue. Conclusion: The expressions LDHA and EGFR are increased in pancreatic cancer tissue, and both of them, especially the LDHA, may influence the prognosis of the patients by regulating the expressions of the signaling molecules associated with pancreatic cancer and the local immune microenvironment.