Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma

SIMPLE SUMMARY: Despite massive research efforts, the mortality of pancreatic ductal adenocarcinoma is still high. In recent years, the tumor microenvironment has been revealed to play a key role in carcinogenesis. Therefore, our study aimed to further characterize the family of cancer-associated fibroblasts. We conducted stainings of four common fibroblast markers in a tissue microarray of 321 patients. Here, we describe three subgroups of expression patterns of these markers which are associated with worse survival. Following further basic research, this could lead to new targeted treatment options for patients with pancreatic ductal adenocarcinoma. ABSTRACT: Purpose: The pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer entities. Effective therapy options are still lacking. The tumor microenvironment possibly bears further treatment possibilities. This study aimed to describe the expression patterns of four established carcinoma-associated fibroblast (CAFs) markers and their correlation in PDAC tissue samples. Methods: This project included 321 patients with PDAC who underwent surgery with a curative intent in one of the PANCALYZE study centers. Immunohistochemical stainings for FAP, PDGFR, periostin, and SMA were performed. The expression patterns of each marker were divided into low- and high-expressing CAFs and correlated with patients’ survival. Results: Tumors showing SMA(high)-, Periostin(high)SMA(high)-, or Periostin(high)SMA(low)PDGFR(low)FAP(high)-positive CAFs demonstrated significantly worse survival. Additionally, a high expression of SMA in PDAC tissue samples was shown to be an independent risk factor for worse survival. Conclusion: This project identified three subgroups of PDAC with different expression patterns of CAF markers which showed significantly worse survival. This could be the base for the further characterization of the fibroblast subgroups in PDAC and contribute to the development of new targeted therapy options against CAFs.