Abstract 7068: Diagnostic and prognostic application of blood and tissue cadherin-17 biomarker in pancreatic cancer

Abstract Background: Pancreatic cancer (PC) is one of the most lethal cancers, with a 5-year overall survival (OS) rate of ∼10%. CA19.9 remains the gold standard biomarker for detecting PC, but its performance is poor, necessitating the exploration of better alternatives. Cadherin-17 (CA17) is overexpressed in several gastrointestinal cancers but shows limited expression in normal tissues, indicating potential diagnostic and prognostic applications in PC. This study aimed to evaluate the diagnostic and prognostic value of CA17 in PC. Methods: We have newly developed an immunohistochemistry (IHC) platform to compare CA17 expression in PC tissues (n = 127), tumor-adjacent tissues (n = 86), and normal pancreatic tissues (n = 22) obtained from 50 retrospective PC cases, alongside a commercial tissue microarray of PC and normal samples. Digital imaging analysis was performed to quantify CA17 expression with an IHC scoring algorithm that combines the percentage of positive cells and staining intensity (M score). Additionally, 86 retrospective plasma samples were collected from asymptomatic donors and 49 patients with paired pre- and post-treatment plasma. CA17 and CA19.9 levels in plasma were measured using our newly developed highly sensitive and specific CA17 immunoassay and a commercial CA19.9 ELISA kit, respectively. Results: Normal pancreatic tissues showed negative CA17 IHC results. A significantly higher CA17 M score was observed in PC compared to both normal and cancer-adjacent tissues (median M score: 5.83, 0.38, 0.85, respectively; p < 0.001). We observed a significant elevation in blood CA17 levels from asymptomatic donors to pre-treatment stage I/II PC patients, with a decrease in CA17 expression in stage III/IV patients (median in ng/mL: 1.45, 7.14, 2.58, respectively; p < 0.0001). Compared to pre-treatment plasma, CA17 levels decreased in post-treatment samples from stages I/II patients, while remaining stable in stages III/IV patients (median in ng/mL: 4.02, 2.42, respectively). Similarly, CA19.9 expression increased progressively from normal donors to stages I/II and stages III/IV patients (median in U/mL: 43, 56, 1446, respectively, p < 0.0001). The ROC curve of the CA17 assay showed an AUC of > 0.92, with both sensitivity and specificity of 86% in detecting stages I/II PC, surpassing CA19.9 (55% and 90%, respectively). Stage III/IV PC patients were stratified based on median-high and low CA17 and CA19.9 levels for a 2-year OS analysis, indicating that combining CA17 and CA19.9 in predicting prognosis outperforms each biomarker individually. Patients with both median-high CA17 and CA19.9 levels had a significantly worse OS than those with median-low CA19.9 (median OS: 7 vs 13 months, p = 0.04). Conclusion: CA17 shows promise as a biomarker for early PC detection and prognosis prediction, potentially improving the screening of high-risk individuals for PC and aiding in disease management. Citation Format: William C. Cho, Wing Shan Yu, Tsz Chun Hon, Elaine T.Y. Cheung, Xiao Qi Wang, Qi-Hua Zhang, Hui-Yan Luo, Dennis Anthony Wong, Wah Cheuck, John M. Luk. Diagnostic and prognostic application of blood and tissue cadherin-17 biomarker in pancreatic cancer [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 7068.