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. • Impact of neoadjuvant chemotherapy (NAT) on molecular characteristics of pancreatic cancer remains unknown. • Proteome profiles of CAFs from treatment-naïve and neoadjuvant chemotherapy-treated pancreatic cancers were compared. Nearly 11% of all proteins in CAFs showed differential abundance following exposure to NAT. • NAT-associated proteome changes in CAFs were mainly related to RNA processing and protein transport. • This exploratory study provides preliminary evidence for NAT-associated changes in pancreatic cancer.
Amrutkar et al. (Wed,) studied this question.