Abstract 1061: Diagnostic application of a novel blood CDH17 immunoassay in the detection of colorectal adenoma

Abstract

Abstract Background: Colorectal cancer (CRC) is the most prevalent gastrointestinal (GI) cancer and contribute significantly to global cancer deaths. The mechanism of CRC development is a complex multistage process from hyperplastic lesions to the formation of adenomas, followed by the progression into malignancy. Hence, early detection during hyperplastic and adenomatous stages warrants new screening tests for effective interception of malignancy progression. Cadherin-17 (CDH17) is a biomarker characterized by its overexpression in several GI cancers, but restricted expression in intestinal mucosal epithelium of normal tissues. We have developed a blood immunoassay using a panel of RUO grade antibodies that unveiled CDH17 as a potential marker with high detection sensitivity and specificity for detecting adenomas. Our immunoassay is useful in identifying high-risk individuals with adenomas that may develop into CRC, which can significantly improve the diagnostic efficiency of colonoscopy that is currently lacking. Methods: The study recruited 66 patients (54 adenoma and 12 hyperplasia) and 39 normal samples (no abnormality by colonoscopy). CDH17 level in plasma samples were measured using the CDH17 immunoassay. Results: The novel CDH17 diagnostic assay showed an operating dynamic range from 90ng to 123pg. We observed a progressive and significant increase in the circulating CDH17 level from normal samples to the hyperplasia group, followed by the adenoma group (mean: 1.66ng/mL, 3.20ng/mL, 4.93ng/mL, respectively P<0.0001). The assay performance by ROC curve demonstrated an AUC of >0.9, with a sensitivity of 85% and specificity of 86%. NPV and PPV were 84% and 87%, respectively. The assay outperforms two market available FIT-DNA tests at predicting adenomas (Table. 1). Conclusion: The novel CDH17 immunoassay is potentially a powerful tool for the detection of aberrant plasma CDH17 expression, improving the surveillance and the detection of high-risk individuals for CRC. CDH17 immunoassay outperforms market availalble FIT-DNA tests at detecting hyperplasia and adenoma FIT-DNA test 1 FIT-DNA test 2 CDH17 blood immunoassay Age 40-74 Age 50-84 Age 45-93 Sensitivity (%) Advanced adenoma 63.5 42.4 85.0 Non-advanced adenoma (i.e Hyperplasia) Unavailable 17.2 58.3 Specificity (%) Normal control (no abnormality by colonoscopy) 87.1 89.8 86.1 NPV (%) Advanced adenoma Unavailable Unavailable 83.8 Non-advanced adenoma (i.e Hyperplasia) Unavailable Unavailable 86.1 PPV (%) Advanced adenoma Unavailable Unavailable 87.2 Non-advanced adenoma (i.e Hyperplasia) Unavailable Unavailable 58.3 Citation Format: Ng Lui, Felix Hon, Stella Sun, Pauline Leung, David Ho, John Moon Luk, Dominic Chi-Chung Foo. Diagnostic application of a novel blood CDH17 immunoassay in the detection of colorectal adenoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1061.