Construction and Validation of a Necroptosis-Related Gene Signature for Predicting Prognosis and Tumor Microenvironment of Pancreatic Cancer

Abstract

Pancreatic cancer (PC) is notorious for its parallel morbidity and mortality rates. Recently, necroptosis, a form of programmed cell necrosis, has gained popularity for its role in tumorigenesis and metastasis. In this study, we explored the expression of necroptosis-related genes in PC and normal pancreatic tissues and identified 52 differentially expressed genes (DEGs). The Cox regression analysis was applied to construct the prognostic risk model, which divided patients into high- and low-risk groups. PC patients in the low-risk group showed a significantly better overall survival (OS) than those in the high-risk group. We further validated the prognostic role in ICGC cohort. Further, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and tumor microenvironment (TME) analysis were used to explore the underlying mechanisms. Notably, based on the gene signature, we revealed that the risk score was strongly related to the sensitivity of chemotherapy. In conclusion, necroptosis-related genes serve as an important immune mediator, and the risk model could be used to predict the survival and to guide the development of precision drugs for patients with PC.