4.7 Article

S100A10, a novel biomarker in pancreatic ductal adenocarcinoma

Journal

MOLECULAR ONCOLOGY
Volume 12, Issue 11, Pages 1895-1916

Publisher

WILEY
DOI: 10.1002/1878-0261.12356

Keywords

DNA methylation; KRAS; pancreatic ductal adenocarcinoma; plasminogen; S100A10

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Funding

  1. Canadian Institutes of Health Research (CIHR) [MOP-123212]
  2. Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2013-4360204]
  3. cancer research training program (CRTP)
  4. Dalhousie University Collaborative Grant

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Pancreatic cancer is arguably the deadliest cancer type. The efficacy of current therapies is often hindered by the inability to predict patient outcome. As such, the development of tools for early detection and risk prediction is key for improving outcome and quality of life. Here, we introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. We demonstrated that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to normal ducts and nonductal stroma. S100A10 mRNA and methylation status were predictive of overall survival and recurrence-free survival across multiple patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness, and in vivo growth of pancreatic cancer cell lines. These findings delineate the clinical and functional contribution of S100A10 as a biomarker in pancreatic cancer.

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