A 15-gene immune, stromal and proliferation gene signature that significantly associates with poor survival in patients with pancreatic ductal adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with dismal survival rates. Tumor microenvironment (TME), comprising of immune cells and cancer-associated fibroblasts, plays a key role in driving poor prognosis and resistance to chemotherapy. Herein, we aimed to identify a TME-associated, risk-stratification gene biomarker signature in PDAC. Experimental Design: The initial biomarker discovery was performed in The Cancer Genome Atlas (TCGA, n=163) transcriptomic data. This was followed by independent validation of the gene signature in The International Cancer Genome Consortium (ICGC, n=95), E-MTAB-6134 (n=288), and GSE71729 (n=123) datasets for predicting overall survival (OS), and for its ability to detect poor molecular subtypes. Clinical validation and nomogram establishment was undertaken by performing multivariate cox regression analysis. Results: Our biomarker discovery effort identified a 15-gene immune, stromal and proliferation (ISP) gene signature that significantly associated with poor OS (HR: 3.90, 95% CI, 2.36-6.41, p