Epigenetic Factors of Colorectal Adenoma in Korean

Overview

This study aims to explore epigenetic factors associated with colorectal adenoma (CRA) in the Korean population. CRA is a key precancerous lesion in the adenoma-carcinoma sequence, and identifying methylated genetic markers may improve early detection and risk stratification for colorectal cancer (CRC). A total of 32 patients undergoing colonoscopic polypectomy will be enrolled. Adenomatous and adjacent normal tissues will be collected for deoxyribonucleic acid (DNA) extraction and bisulfite conversion. Quantitative methylation-specific polymerase chain reaction (qMSP) and Sanger sequencing will be used to assess the methylation status of candidate genes (SFRP2, TFPI2, SEPT9, and SDC2). Stool samples will also be analyzed by whole-genome sequencing (WGS) to evaluate microbiome and genetic profiles. The study seeks to determine whether methylation levels of these genes are significantly elevated in adenoma tissue compared with normal mucosa, thereby identifying potential biomarkers for colorectal neoplasia surveillance and personalized colonoscopy follow-up intervals.

Colorectal cancer (CRC) is one of the most common malignancies in Korea, ranking second in national cancer incidence statistics. Most CRCs arise through the adenoma-carcinoma sequence, in which epigenetic and genetic alterations play critical roles. Identifying methylated genetic markers in colorectal adenoma may provide insights into early carcinogenic mechanisms and enable more individualized surveillance strategies after polypectomy. This study focuses on exploring epigenetic factors-particularly DNA methylation patterns-associated with colorectal adenoma in Korean patients. A total of 32 participants undergoing colonoscopic polypectomy will be recruited. From each participant, both adenomatous tissue and adjacent normal mucosa (approximately 5 millimeters (mm) in size) will be collected. Stool samples will also be obtained for microbiome and genomic analysis. DNA extracted from tissue and stool samples will undergo bisulfite conversion using the EZ DNA Methylation-Gold Kit (Zymo Research). Quantitative methylation-specific polymerase chain reaction (qMSP) will be performed to evaluate promoter methylation levels of four candidate genes-SFRP2 (Secreted Frizzled Related Protein 2), TFPI2 (Tissue Factor Pathway Inhibitor 2), SEPT9 (Septin 9), and SDC2 (Syndecan 2)-that have previously shown potential as colorectal neoplasia biomarkers. Selected samples will also undergo Sanger sequencing for CpG-level methylation profiling. Stool DNA will be analyzed through whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform to assess microbial composition and genetic context. Methylation indices (MtI) and percentage of methylated reference (PMR) values will be calculated and compared between adenoma and adjacent normal tissues. Receiver operating characteristic (ROC) curve analysis will determine the sensitivity and specificity of each gene as a potential biomarker. By identifying methylated genes that are significantly upregulated in adenomatous tissues, this study aims to propose candidate epigenetic markers for predicting the recurrence or malignant transformation of colorectal adenoma. The findings may contribute to refining post-polypectomy surveillance intervals and supporting precision prevention strategies in CRC.