Abstract
OBJECTIVE: To explore the performance of a predictive model based on plasma multigene methylation testing in the early diagnosis of colorectal cancer (CRC). METHODS: A total of 688 patients with suspected CRC who underwent diagnostic examination at the Affiliated Hospital of Xuzhou Medical University between July 2022 and June 2024 were enrolled. The plasma methylation status of 5 genes, including SEPTIN9 (septin 9), BCAT1 (branched chain amino acid transaminase 1), IKZF1 (IKAROS family zinc finger 1), BCAN (brevican), and VAV3 (vav guanine nucleotide exchange factor 3), was assessed before pathological biopsy. The negative or positive results of the methylation testing of the 5 genes were compared with the clinical pathological diagnosis results of the same participants to construct a predictive model based on the methylation status of SEPTIN9, BCAT1, IKZF1, BCAN, and VAV3 genes, and the performance of the predictive model in the early diagnosis of CRC patients was evaluated. RESULTS: Of the 688 patients, 48 had a pathologically confirmed diagnosis of colorectal carcinoma. The diagnostic performance of a single-gene methylation status for CRC was as follows: SEPTIN9 showed a sensitivity of 47.92%, specificity of 96.72%, and AUC of 0.804 (95% CI: 0.672-0.899); BCAT1 showed a sensitivity of 52.08%, specificity of 96.88%, and AUC of 0.753 (95% CI: 0.702-0.864); IKZF1 showed a sensitivity of 50.00%, specificity of 98.28%, and AUC of 0.740 (95% CI: 0.635-0.881); BCAN showed a sensitivity of 33.33%, specificity of 98.75%, and AUC of 0.690 (95% CI: 0.572-0.785); VAV3 showed a sensitivity of 35.42%, specificity of 97.66%, and AUC of 0.686 (95% CI: 0.597-0.734). A diagnostic model integrating the 5 genes achieved a sensitivity of 85.42%, specificity of 93.40%, and AUC of 0.916 (95% CI: 0.835-0.972). The diagnostic sensitivities of the model for CRC of different stages were 85.71% for stage Ⅰ, 92.86% for stage Ⅱ, 78.95% for stage Ⅲ, and 87.50% for unstaged cases. CONCLUSION: A diagnostic model based on the methylation levels of the SEPTIN9, BCAT1, IKZF1, BCAN, and VAV3 genes in plasma demonstrates good diagnostic performance for CRC, particularly in early-stage cases.