Abstract: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 CSF1R mRNA, and LDHA was positively correlated with the expressions of FOXM1, CSF1 and CSF1R (all P<0.05). The protein expression abundances of EGFR, LDHA, P38, FOXM1 and CSF1R 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.