Identification of a fibroblast-derived gene signature reveals prognostic and therapeutic insights in pancreatic cancer

Abstract

Fibroblasts play a crucial role in the progression of pancreatic ductal adenocarcinoma (PDAC). This study aimed to develop a prognostic model based on fibroblast-specific gene signatures and identify key genes that may serve as therapeutic targets. Single-cell RNA sequencing data from PDAC and adjacent normal tissues were analyzed using high-dimensional weighted gene co-expression network analysis, and a prognostic signature was constructed using LASSO Cox regression and validated across multiple cohorts. Our findings revealed distinct fibroblast clusters enriched in PDAC and led to the development of a fibroblast-related prognostic signature comprising 14 key genes. The fibroblast-related risk score effectively stratified patients into high-risk and low-risk groups, revealing differences in immune cell infiltration, response to immune checkpoint blockade therapy, and sensitivity to chemotherapeutic drugs. This study presents a novel fibroblast-associated prognostic model with significant clinical utility in predicting PDAC patient outcomes.