Proteomic characterization of primary pancreatic fibroblasts derived from neoadjuvant chemotherapy treated versus treatment-naïve PDAC.

Neoadjuvant chemotherapy (NAT) is increasingly used in the treatment of pancreatic ductal adenocarcinoma (PDAC). However, the actual molecular impact of NAT on the tumor remains unknown, particularly on the cancer-associated fibroblasts (CAFs) remains largely unknown. Here, mass-spectrometry (MS)-based proteomic profiling of primary CAFs derived from treatment-naïve (TN) and NAT-treated resected PDAC (n = 10 in each group) was conducted to explore potential NAT-associated changes. Differentially abundant proteins (DAPs; p < 0.05) in NAT versus TN CAFs accounted for 10.6% of all 5438 proteins mapped by MS. According to gene ontology analysis, DAPs with higher abundance (273) in NAT versus TN were involved in protein transport and carbohydrate metabolism, while DAPs with lower abundance (305) were mainly related to RNA processing. Protein-protein interactions identified several cluster networks of closely linked DAPs. Exploring the correlation between DAPs abundance and survival identified a negative correlation for 30 of 42 DAPs in NAT group. In addition, several proteins were found to be differentially abundant among different NAT regimens. In conclusion, this exploratory study reveals significant NAT-associated changes in CAF proteome profiles, which are related to the fundamental biological processes of RNA processing and protein transport. Further validation of these preliminary findings using a large independent cohort is needed.