Abstract 682: PCDHGB10: a unique, sensitive, and specific serum cfDNA methylation biomarker for stomach adenocarcinoma diagnosis

Abstract Serum cell-free DNA (cfDNA) methylation has demonstrated its potential in detecting and screening for multiple cancers, offering a critical window for identifying patients eligible for effective treatment. Our objective was to evaluate the efficacy of high methylation-sensitive restriction enzyme combined quantitative PCR (MSRE-qPCR) in identifying a serum cfDNA methylation biomarker for a spectrum of cancer types. We initially developed a 6-gene panel comprising 11 pan-cancer cell-differentially methylated regions across 15 prevalent cancer types, utilizing data from the TCGA methylome database (n = 6981). This panel was then validated using MSRE-qPCR on serum cfDNA samples from 825 participants, encompassing 632 cancer patients across 11 cancer types and 193 healthy controls, collected from multiple cancer centers in China. We assessed the specificity and sensitivity of the panel for diagnosing individual cancers at multiple sites, including the colorectum, esophagus, stomach, liver, lung, ovary, lymphoma, cervix, endometrium, nasopharynx, and pancreas. Among the 11 cancer types, stomach adenocarcinoma (STAD) demonstrated the highest sensitivity and specificity for DNA methylation-based diagnosis in real-world scenarios. PCDHGB10 methylation particularly stood out for STAD diagnosis, achieving a sensitivity of 93.16% and specificity of 88.24% in the training cohort, and 84.09% sensitivity and 96.67% specificity in the validation cohort. For early-stage (I and II) patients, PCDHGB10 sensitivity was 78.48%, rising to 86.89% in late-stage patients. In contrast, PCDHGB10 methylation showed suboptimal diagnostic performance (less than 65% sensitivity) in the other 10 cancer types. This extensive public database and clinical validation study underscores the role of PCDHGB10 methylation as a highly sensitive, specific, and distinctive serum cfDNA methylation biomarker for STAD diagnosis, with particular promise for early-stage detection. Citation Format: Donghong Zhang, Chaoyan Niu, Daoyu Yan, Ruo-Pan Huang. PCDHGB10: a unique, sensitive, and specific serum cfDNA methylation biomarker for stomach adenocarcinoma diagnosis [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 682.