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

Karl Knipper; Alexander I Damanakis; Yue Zhao; Christiane J Bruns; Thomas Schmidt; Felix C Popp; Alexander Quaas; Su Ir Lyu; PANCALYZE Study Group

doi:10.3390/cancers15072049

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

Cancers (Basel). 2023 Mar 30;15(7):2049. doi: 10.3390/cancers15072049.

Authors

Karl Knipper¹, Alexander I Damanakis¹, Yue Zhao¹, Christiane J Bruns¹, Thomas Schmidt¹, Felix C Popp¹, Alexander Quaas², Su Ir Lyu²; PANCALYZE Study Group

Affiliations

¹ Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany.
² Institute of Pathology, University Hospital of Cologne, Faculty of Medicine, University of Cologne, 50937 Cologne, Germany.

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^highSMA^high-, or Periostin^highSMA^lowPDGFR^lowFAP^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.

Keywords: pancreatic ductal adenocarcinoma; personalized medicine; subgroups of fibroblasts.

Grants and funding

This research received no external funding.