Abstract 3346: Evaluation of a serum-based test integrating tumor tissue and gut microbiome derived metabolites for diagnosis of advanced colorectal adenoma

Abstract Background: Detection and endoscopic excision of colorectal precancerous lesions (advanced adenoma, AA) has been recognized as an effective way to prevent the occurrence of colorectal cancer (CRC) and reduce CRC induced mortality. Current DNA-based (mutations or methylations) tests exhibited compromised efficiency for AA diagnosis due to the late appearance of tumor-derived DNA biomarkers into stool or blood samples during tumorigenesis. Here, by integrating metabolic biomarkers associated with tumor tissue and colorectal neoplasia related gut microbiota, we established the serum metabolites-based test and examined its ability to detect advanced adenoma patients from normal, hyperplastic polyps and low-risk adenoma individuals. Methods: Consensus participants undergoing coloscopy were enrolled in this prospective study, and the result of colonoscope examination and histopathology from biopsied lesions were used as gold standard (ChiCTR2200058078). Serum metabolites were quantified by pseudo-targeted metabolomics based on LC-MS/MS method. By integrating abundances of these serum metabolites associated with tumor tissue and colorectal neoplasia related gut microbiota, a diagnostic model was established, and its performance for detecting advanced adenoma was validated using leave-one-out cross-validation. Results: In total, 803 participants, including 178 normal individuals, 167 patients with hyperplastic polyps, 203 patients with low-risk colorectal adenoma and 255 advanced colorectal adenoma patients, were enrolled in this study and subjected to the serum metabolites-based test. The diagnostic model achieved an AUC of 0.80 (95% CI: 0.77-0.83) for advanced adenoma, with a sensitivity of 44.7% at 88.9% specificity. Additionally, we also separately analyzed its performances for advanced adenoma with different histological subtypes, achieving a sensitivity of 37.0% for tubulous adenoma and a sensitivity of 53.3% for adenoma with villous structure, respectively. As for advanced adenoma with high-grade dysplasia, the model could achieve a sensitivity of 61.2%. In comparation, sensitivities of all current tests for advanced colorectal adenoma, either fecal or blood based, were less than 45% at a similar specificity. Conclusions: Based on integrating metabolic biomarkers associated with both tumor tissue and colorectal neoplasia related gut microbiota, we developed a novel blood-based test that can detect advanced colorectal adenoma with higher accuracy than all current fecal or blood-based tests. Citation Format: Jingyuan Xiang, Longsong Li, Xingting Guo, Xiaowei Li, Kai Lin, Liuyang Yang, Xudong Dai, Enqiang Linghu, Ningli Chai. Evaluation of a serum-based test integrating tumor tissue and gut microbiome derived metabolites for diagnosis of advanced colorectal adenoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3346.