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Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.

ABSTRACT: Previous studies have suggested that ?-adrenergic signaling may regulate the growth of various cancers. The aim of our study is to investigate the association between the incidental use of beta-blockers for various conditions on the overall survival of patients with pancreatic ductal adenocarcinoma (PDAC). Patients with histologically-confirmed PDAC between 2007 and 2011 were extracted from Surveillance, Epidemiology, and End Results registry (SEER)-Medicare linked database. Kaplan Meier and multivariable Cox Proportional-Hazard models were used to examine the association between beta-blocker usage before diagnosis and overall survival adjusting for appropriate confounders. As an additional analysis we also examined continuous beta-blocker use before and after diagnosis. From 2007 to 2011, 13,731 patients were diagnosed with PDAC. Of these, 7130 patients had Medicare Part D coverage in the 6-month period before diagnosis, with 2564 (36%) of these patients using beta-blockers in this period. Patients receiving beta-blockers had a mean survival time of 5.1 months compared to 6 months for non-users (p??0.05). After stratification by receptor selectivity, this lack of association with survival persisted (p?>?0.05 for all). As a subgroup analysis, looking at patients with continuous Medicare Part D coverage who used beta-blockers in the 6-month period before and after cancer diagnosis, we identified 7085 patients, of which 1750 (24.7%) had continuous beta blocker use. In multivariable analysis, continuous beta-blockers usage was associated with improved survival (Hazard Ratio (HR) 0.86, 95%, Confidence Interval (CI) 0.8-0.9, p?

SUBMITTER: Yang A

PROVIDER: S-EPMC7807087 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Project description: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 TGF?-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.

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Beta-blockers have no impact on survival in pancreatic ductal adenocarcinoma prior to cancer diagnosis.

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