The Senescence-Related Signature Predicts Prognosis and Characterization of Tumor Microenvironment Infiltration in Pancreatic Cancer.

Abstract

Senescence is thought to be an imperative effect on the development of cancer. However, few studies pay an attention to the senescence-associated genes in pancreatic cancer (PC). The prognostic value of senescence-related genes (SRGs) and their involvement in tumor microenvironment (TME) in the PC remain obscure. The aim of this research was to investigate the prognostic role of senescence-associated genes and their affection in TME in PC. The transcriptome and clinical information of PC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Two SRG-mediated molecular clusters were comprehensively identified. In total, data from the 285 PC patients were randomly used to develop a senescence-associated gene signature in the training set and verified in the validation set. Immune microenvironment analysis pertained to senescence-related genes was performed. A SRG_score including five senescence-associated genes was established to separate PC patients into two risk groups. High-risk patients had worse overall survival than low-risk patients. The result of the multivariate Cox regression analysis identified the risk score and stage as independent prognostic factors for PC patients. Receiver operating characteristic curve (ROC) analysis confirmed the credible predictive ability of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.746 at 1 year, 0.781 at 3 years, and 0.868 at 5 years in the training set and 0.653 at 1 year, 0.755 at 3 years, and 0.785 at 5 years in the validation set. Moreover, the SRG_score was associated with TME, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. This study found that the novel SRG_score could be an independent prognostic target for PC patients. Senescence-associated genes had a vital impact on the immune microenvironment and the treatment of PC patients.