Abstract 3688: A novel biomarker for pancreatic cancer, sTRA, and CA19-9 define separate subpopulations of PDAC cells with distinctions in behavior and molecular characteristics

Abstract

Abstract Cancer cells in pancreatic ductal adenocarcinomas (PDACs) exhibit tremendous diversity in behavior and phenotype, but no biomarkers are available to identify subtypes with clinically significant differences in behavior. We recently identified a new marker of pancreatic cancer, called sTRA, that is expressed on cancer cells with different morphologies and molecular characteristics than cancer cells expressing the biomarker CA19-9. Here we tested the hypothesis that the two types of cells have differences between them in behavior, gene expression, and associations with outcome. In cell line models, sTRA-expressing cancer cells were more resistant to drugs, more invasive, and slower-growing than the CA19-9-expressing cells. Patient-derived xenograft tumors produced either CA19-9 or sTRA, and RNA-seq analysis revealed significant, nonrandom differences between the sTRA-expressing and CA19-9-expressing tumors. Each subpopulation was found in lymph nodes or livers with levels that significantly correlated with their matched primary tumors. In an analysis of two tissue microarrays covering 45 and 41 patients, the tumors containing high levels of sTRA-expressing cancer cells had the shortest survival times. These data support the existence of two distinct subtypes of PDAC cells, respectively marked by CA19-9 and sTRA. Together the markers could have value for predicting the behavior of tumors and for isolating, characterizing, and targeting specific subtypes of cancer cells. Citation Format: Daniel Barnett, Ying Liu, ChongFeng Gao, Luke Wisniewski, Katie Partyka, Anna Barry, Galen Hostetter, Aatur Singhi, Randall E. Brand, Richard R. Drake, Brian B. Haab. A novel biomarker for pancreatic cancer, sTRA, and CA19-9 define separate subpopulations of PDAC cells with distinctions in behavior and molecular characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3688.