Abstract 2526: Non-invasive biomarker discovery and validation for the early detection of pancreatic cancer

Abstract Introduction: Pancreatic malignancies are the fourth leading cause of all cancer-related deaths in the United States and this high mortality rate can be attributed to a lack of diagnostic tests for early detection. A majority of patients with pancreatic ductal adenocarcinoma (PDAC) present with advanced disease due to a lack of specific symptoms suggesting that early detection may significantly improve patient outcomes. CA19-9, the only FDA-approved blood biomarker for PDAC, is insufficiently sensitive and specific for detection or surveillance. The goal of our study is to discover and validate non-invasive biomarkers for early PDAC detection. Methods: We have established a biomarker discovery initiative whose objective is to identify differentially expressed proteins in the urine of cancer patients and validate their diagnostic and prognostic efficacy. For PDAC, our target population(s) include Stage I or II PDAC patients, high risk individuals (HRI, individuals under surveillance for genetic or familial causes) and age- and sex-matched healthy controls (HC). In this study, we have analyzed urinary markers including CTGF, CYR61, TIMP1 and ADAM12, proteins reported to contribute to PDAC development and progression, with the goal of determining their potential to differentiate early (Stage I-II) PDAC from HC, HRI and advanced disease (Stage III-IV). Results: Urinary TIMP-1 (uTIMP-1) levels were significantly (∼19-fold) higher in PDAC patients (all stages; n=64) compared to HC (n=60) and significantly (∼3.5-fold) higher in PDAC patients (all stages) compared to those with benign pancreatic conditions including IPMN (intraductal papillary mucinous neoplasm) or pancreatic cysts (n=10). When comparing the HRI cohort (n=70, no evidence of disease, NED) to all groups, we found that uTIMP-1 levels were significantly (∼13-fold) higher in PDAC patients (all stages) compared to those at high-risk (n=37). uADAM12 levels were significantly (∼17-fold) higher in PDAC patient samples (all stages) compared to those from HC and significantly (∼1.6-fold) higher in PDAC patients compared to those with benign disease, whereas uADAM12 levels were significantly (∼5-fold) higher in PDAC patients (all stages) compared to the HRI cohort. While CYR61 levels did not differ between any of the groups tested, CTGF levels were significantly (∼700-fold) higher in PDAC patients (all stages) compared to patients with benign disease and significantly (∼1500-fold) higher in PDAC patients (all stages) compared to the HRI cohort. Conclusions: Taken together, our results suggest that the non-invasive detection of uTIMP-1, uADAM12 and uCTGF levels may have diagnostic value in the early detection and/or clinical monitoring of disease status in patients with PDAC. [The authors gratefully acknowledge the support of the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation and the Nile Albright Research Foundation] Citation Format: Roopali Roy, Rama Aldakhlallah, Stephen Cobbs, Noundy Mazile, Kiana Mahdaviani, Matthew Kulke, Christopher Heaphy, Jeanette Dupree, David Zurakowski, Sarah Danielle Legrand, Erkut Borazanci, Marsha A. Moses. Non-invasive biomarker discovery and validation for the early detection of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2526.