Identify novel inflammation-related prognostic signature in pancreatic cancer patients.

Abstract

Pancreatic cancer (PC) is a malignant tumor of the digestive system with a poor prognosis. PC patients with pancreatitis have a worse prognosis. But nobody reported the relationship between inflammation and prognosis in PC. Based on this, we are going to explore inflammation-related prognostic signature to predict patients' survival and potential therapeutic target. We screened gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was performed to identify differentially expressed genes (DEGs) between tumor and normal tissues with P value < .05. Univariate and multivariate Cox regression analysis was applied to identify possible prognostic inflammation genes and establish an inflammation-related risk score system, which was validated by Kaplan-Meier and Receiver operating characteristic (ROC) curves. Finally, we used the TISIDB database to predict targeted drugs for up-regulated gene hepatocyte growth factor receptor (MET) and used AUTODOCK software for molecular docking. We built a prognostic model consisted of 3 inflammation-related genes (tumor necrosis factor receptor associated factor 1/TFAR1, tyrosine kinase 2/TYK2, MET). According to the median value of those genes' risk score, PC patients were ranked into high- (88) and low-risk (89) groups. Then, the results of the Kaplan-Meier curves and the area under the curve (AUC) of the ROC curves showed this model had a good predictive power (P < .001, AUC = 0.806). The result of human protein atlas (HPA) database showed the expression of TRAF1 and TYK2 were low in pancreatic cancer, the expression of MET was high. TISIDB database founded brigatinib could target to MET. And AUTODOCK showed brigatinib had a nice docking with MET. Taken together, our study suggested that inflammation-associated prognostic signature might be used as novel biomarkers for predicting prognosis in PC patients and potential therapeutic target of the disease.