Evaluation of Multigene Methylation for Blood-Based Detection of Colorectal Cancer

<b><i>Background:</i></b> Early screening for colorectal cancer (CRC) has the potential to improve patient prognosis, but current screening methods are limited. In this prospective study, we aimed to evaluate the multigene (<i>Septin9, SDC2, KCNQ5,</i> and <i>IKZF1</i>) detection in patient plasma for CRC diagnosis. <b><i>Methods:</i></b> Overall, 67 participants were enrolled, including 31 patients with CRC, 17 patients with colorectal polyp, and 19 normal controls who underwent colonoscopy. Carcinoembryonic antigen (CEA) and <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> methylation tests were performed. Sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of each biomarker. The association between positive rates of methylated <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> and the clinicopathological characteristics of CRC was also analyzed. <b><i>Results:</i></b> The positive rate of multigene methylation detection was 87.1% (27/31) in patients with CRC, which was higher than single indicators: CEA (51.61%, 16/31), <i>Septin9</i> (41.94%, 13/31), <i>SDC2</i> (41.94%, 13/31), <i>KCNQ5</i> (58.06%, 18/31), and <i>IKZF1</i> (32.26%, 10/31). In the colorectal polyp group, the rate of multigene methylation detection is 88.24% (15/17), which was also higher than single indicator: CEA (17.65%, 3/17), <i>Septin9</i> (11.76%, 2/17), <i>SDC2</i> (64.71%, 11/17), <i>KCNQ5</i> (58.82%, 10/17), and <i>IKZF1</i> (35.29%, 6/17). The ROC curves further showed better diagnostic value of the multigene test for CRC than any single gene. Correlation analysis found that the positive rate of the test was not affected by patients' clinicopathologic characteristics. <b><i>Conclusion:</i></b> The combination of methylated <i>Septin9, SDC2, KCNQ5</i>, and <i>IKZF1</i> tests is preferable to individual gene tests for patients with CRC and polyp.