A novel CAF-related gene signature for prognostic and immunotherapy response prediction in PDAC based on single-cell RNA-seq and bulk RNA-seq data.

Increasing evidence shows that cancer-associated fibroblasts (CAFs) contribute to tumor progression, create an immunosuppressive microenvironment, and promote resistance to immunotherapy. However, the CAF-related gene signature in pancreatic ductal adenocarcinoma (PDAC) remains largely unexplored. In our study, we constructed a nine-gene CAF-related signature and found that it strongly correlated with the prognosis of PDAC patients in different cohorts. Subsequently, we found that the CAF-related gene signature was associated with the genomic alteration landscape, immune infiltration landscape and responsiveness to immunotherapy. GJB2 had the highest coefficient in our CAF-related gene signature, thus we explored the role of GJB2 in the interactions between CAFs and PDAC cells. The results showed that conditioned medium (CM) derived from the GJB2 knockdown group could suppress the malignant phenotype of PANC1 and MIAPaCa2 cells. In summary, this CAF-related gene signature is useful for prognosis prediction and precision therapy of PDAC patients.