Abstract 4967: Identifying prognostic biomarkers and risk factors contributing to racial disparity and high mortality in pancreatic cancer at Sentara-EVMS-VOA

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and tthe deadliest form of human cancer. Early detection and curative intervention regimens are unmet needs in the clinic. The PDAC incidence and mortality have doubled from 1990-2017. Oncogenic K-RAS mutation is universally activated in PDAC tumors, that drive tumor malignancy, early relapse, chemo-resistance, metastasis, and dismal survival. In this study, we examine whether SIAH, an evolutionarily conserved E3 ligase that is the most downstream signaling gatekeeper of the EGFR/K-RAS pathway, has prognostic value in PDAC. Methods: A cohort of 1,156 patients with PDAC, diagnosed at Sentara-VOA between 2001-2016 was analyzed to determine the association of SIAH expression with TNM staging, treatment efficacy, and survival prediction. SIAH expression was calculated by the average immunohistochemical (IHC) scores from two clinical pathologists in 148 operable PDAC patients, including 34 neoadjuvant chemotherapy (NACT)-treated residual tumors and 114 untreated primary tumors. Results: Among 1,156 PDAC patients, 354 of them were operable and 802 of them are inoperable. A comparison of the 5-year survival rates showed that our local cohorts were underperforming to that of the national average from 2001 to 2016. Following the PDAC clinical procedural standardization at Sentara Cancer Network, our local 5-year survival rates have started to improve steadily, and it has approached the national standards after 2010. Analysis of the SIAH expression in 34 NACT-treated residual tumors showed that low SIAH expression (< 5%) correlated with a longer survival than those with higher SIAH expression (>5%). Discussion: Among 1,156 PDAC patients, 32.8% of the white patients and 27.4% of Black/AA patients received surgical resection. A 5.4% difference of the two-race groups in the operable cohort suggested that Black/AA patients are more likely to present with advanced and unresectable PDAC. The narrowing of the survival gap between the local and national cohorts reflects a better PDAC management plan, treatment standardization, and timely implementation of effective treatment modalities, including the Whipple procedure, and NACT regimens for all the eligible operable PDAC patients, at Sentara Hospitals after 2010. We found that persistent high SIAH expression in residual tumors post-NACT is indicative of chemo-resistant tumor cells at the 1st-line neoadjuvant setting, and SIAH may be prognostic to identify high-risk PDAC patients who are prone to develop early relapse and suffer poor survival clinically. Citation Format: Shoba Abraham, Fatima Chaudhry, Zakary Kolkey, Richard Hoefer, Amy Tang. Identifying prognostic biomarkers and risk factors contributing to racial disparity and high mortality in pancreatic cancer at Sentara-EVMS-VOA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4967.