Pancreatic ductal
adenocarcinoma (PDAC) is a highly lethal disease with a dismal prognosis. However, while most patients die within the first year of diagnosis, very rarely, a few patients can survive for >10 years. Better understanding the molecular characteristics of the pancreatic
adenocarcinomas from these very-long-term survivors (VLTS) may provide clues for
personalized medicine and improve current
pancreatic cancer treatment. To extend our previous investigation, we examined the
proteomes of individual pancreas
tumor tissues from a group of VLTS patients (survival ≥10 years) and short-term survival patients (STS, survival <14 months). With a given analytical sensitivity, the
protein profile of each pancreatic
tumor tissue was compared to reveal the
proteome alterations that may be associated with
pancreatic cancer survival. Pathway analysis of the differential
proteins identified suggested that MYC, IGF1R and p53 were the top three upstream regulators for the STS-associated
proteins, and VEGFA,
APOE and TGFβ-1 were the top three upstream regulators for the VLTS-associated
proteins. Immunohistochemistry analysis using an independent cohort of 145 PDAC confirmed that the higher abundance of
ribosomal protein S8 (RPS8) and prolargin (PRELP) were correlated with STS and VLTS, respectively. Multivariate Cox analysis indicated that 'High-RPS8 and Low-PRELP' was significantly associated with shorter survival time (HR=2.69, 95% CI 1.46-4.92, P=0.001). In addition,
galectin-1, a previously identified
protein with its abundance aversely associated with
pancreatic cancer survival, was further evaluated for its significance in cancer-associated fibroblasts. Knockdown of
galectin-1 in
pancreatic cancer-associated fibroblasts dramatically reduced cell migration and invasion. The results from our study suggested that PRELP,
LGALS1 and RPS8 might be significant prognostic factors, and RPS8 and
LGALS1 could be potential therapeutic targets to improve
pancreatic cancer survival if further validated.