A multi-gene blood-based methylation assay for early diagnosis of colorectal cancer

Early detection for colorectal cancer (CRC) can enhance the patient prognosis. We aimed to validate the combined multi-gene detection in plasma of Septin9, SDC2, KCNQ5, and IKZF1 for early diagnosing of CRC in this prospective study.

Overall, 124 participants including 45 CRC patients, 8 advanced adenoma patients, 34 small polyp patients, and 37 normal controls who underwent colonoscopy were enrolled. The carcinoembryonic antigen (CEA) test and methylation tests for Septin9, SDC2, KCNQ5, and IKZF1 were performed. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were utilized to evaluate the diagnostic value of each biomarker. Additionally, the association between the positive rates of methylated Septin9, SDC2, KCNQ5, and IKZF1 and the clinicopathological characteristics of CRC was also analyzed.

The positive detection rate of multi-gene methylation in CRC patients was 86.67%, for stage I and stage II patients, the positive rates were 90.91% and 87.50%, both of which were significantly higher than CEA, which had rates of 55.56%, 18.18% and 56.25% for the corresponding stages. In patients with advanced adenomas and small polyps, the positive rates for the four-gene combined test were 62.50% and 52.94%, respectively, which were markedly higher than the CEA rates of 12.50% and 14.71%. AUC of the ROC curve indicated that the diagnostic value of the multi-gene test for CRC was superior to that of any single gene. Correlation analysis revealed that the positive rate of the test was not affected by patients' clinicopathological characteristics.

A combination of methylated Septin9, SDC2, KCNQ5, and IKZF1 test has the potential for early diagnosis of CRC patients, advanced adenoma patients, and small polyp patients.