Clinical application value of MYO1-G methylation in plasma circulating tumor DNA combined with fecal occult blood test for early screening of colorectal cancer.

[OBJECTIVE] Multiple screening strategies are guideline-endorsed for colorectal cancer (CRC). We investigated the clinical value of plasma circulating tumor DNA (ctDNA) MYO1-G methylation and fecal occult blood test (FOBT) combination in CRC screening.

[METHODS] Participants were allocated to the healthy control, colorectal polyp (Col-pol), and CRC groups. Blood and stool samples were collected at least 1 day before colonoscopy, and plasma ctDNA MYO1-G methylation was measured. The quantitative FOBT was conducted using a fully-automatic OC-Sensor analyzer. CRC patients were assigned to the high-methylation (n = 34) and low-methylation (n = 33) groups as per the median value of methylation ratio of ctDNA MYO1-G. The diagnostic value of plasma ctDNA MYO1-G methylation plus FOBT and the correlation between sensitivity and clinical variables were analyzed.

[RESULTS] Col-pol or CRC patients exhibited raised plasma ctDNA MYO1-G methylation copy number and methylation ratio, with CRC patients showing a higher ratio. There was no significant difference in the total copy number of MYO1-G among the three groups. Plasma ctDNA MYO1-G methylation plus FOBT could distinguish Col-pol (AUC = 0.823) and CRC (AUC = 0.955) patients from controls, and discriminate CRC from Col-pol (AUC = 0.844), displaying higher performance than FOBT. The sensitivity of their combination for assessing CRC was independent of gender, age, tumor size, clinical TNM stage, differentiation degree, pathological pattern, and histology, whereas FOBT sensitivity varied by age (p = 0.04), with higher sensitivity in CRC patients > 50 years old.

[CONCLUSION] Plasma ctDNA MYO1-G methylation plus FOBT exhibits high diagnostic value for Col-pol/CRC.