Abstract A033: Mapping age-specific biomarker dynamics in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal age-related disease, with a median age of diagnosis over 70 years. Understanding age-dependent aberrations in the blood proteome might facilitate early detection, prognosis, and treatment personalization of PDAC. In this study, we aim to decipher novel clinically relevant biomarkers that distinguish between younger and older PDAC patients. To do this, we used a syngeneic orthotopic PDAC animal model where we implanted murine KPC cells (KRasG12D/+; Tp53R172H/+) into the pancreata of age-restricted groups of young (6-8 weeks) and old (80-84 weeks) C57BL/6 mice. Our previous findings demonstrated accelerated tumor growth and an increased metastatic burden in older mice relative to younger ones. Proteomic analysis of plasma from tumor-bearing young and old mice revealed an array of upregulated age-specific circulating proteins relative to their non-tumor, age- and sex-matched controls. Using a threshold of >2-fold change and p<0.05, our analysis identified 22 and 24 proteins preferentially increased in young and old mice, respectively. To ascertain the clinical relevance of our findings in humans, we analyzed expression profiles of selected proteins in human PDAC datasets from The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses have highlighted proteins involved in an array of processes as key candidates, which are consistent with our mouse proteomics findings. These candidate proteins show higher expression levels in human tumors compared to healthy controls and exhibit significant correlations with patient age and overall survival. Our ongoing validation studies have identified a protein from the immunoglobulin superfamily of cell adhesion molecules as a potential biomarker of PDAC, particularly relevant for younger patients. We are currently conducting age-dependent characterization of cell adhesion molecules to understand their role in intercellular crosstalk between cancer and stromal cells, immune surveillance, and metastasis. Citation Format: Priyanka Gupta, Karen Duong-Polk, Rabi Murad, Cosimo Commisso. Mapping age-specific biomarker dynamics in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A033.