A multi-omics CRC screening practice combined primary medical accessible SDC2 methylation and home self-test stool hemoglobin/transferrin test: a prospective, real world, community-based study

Screening is an important way to reduce the incidence and mortality of colorectal cancer (CRC), yet most of the screening-eligible Chinese population is not up to date with screening. Primary medical accessible SDC2 bisulfite-free methylation detection and home self-test stool hemoglobin (FIT)/transferrin (TF) test has the potential to improve screening coverage and effectiveness, reduce the incidence and mortality of CRC. In a prospective, real-world, community-based CRC screening study was implemented in Hefei, Anhui province, China, recruiting asymptomatic individuals aged 45-74 years. All eligible participants were included to complete the following tests: CRC risk-adapted screening, home self-test stool FIT/TF test, SDC2 methylation detection based on innovative STEM-PCR platform. Based on the risk-stratification, high-risk subjects were referred for colonoscopy. All subjects with FIT, TF and SDC2 positive result were referred for colonoscopy. A WeChat mini-program is used to collect CRC-related questionnaire responses, FIT/TF test results, and SDC2 methylation loci status closely related to colorectal cancer, as well as to notify participants of their screening outcomes. The detection rate of advanced neoplasm was the primary outcome. Secondary objectives included the feasibility of home-based FIT/TF self-testing, the accessibility of the established SDC2 bisulfite-free methylation detection method at the primary medical institution. This study was approved by the ethics committees of Shanghai Jiao Tong University and Anhui Provincial Cancer Hospital. Of 18,872 individuals were eligible and 16,878 completed CRC risk-adapted screening, FIT/TF test, and stool SDC2 methylation detection. Overall, 5,629 (33.4%) participants evaluated high-risk, or tested positive for FIT/TF or SDC2 methylation status, and 1,241 (22%) underwent colonoscopy (the results of the colonoscopy are still being compiled). Among these, 603 (48.5%) had abnormal colonoscopy findings, 525 (42.3%) had CRC or precancerous lesions, 11 (0.9%) were diagnosed with CRC, 117 (9.4%) had advanced precancerous lesions, 277 (22.3%) had nonadvanced adenomas, 179 (14.4%) has polyps and other colorectal disease, and 31 (2.5%) showed colorectal neoplasm but lack pathological diagnosis. Compared to the traditional CRC screening protocol of risk-adapted screening plus FIT test, the additional of TF can increase the detection rate of advanced neoplasm by 2.8% and the detection rate of nonadvanced adenomas by 6.3%. What’s more, the additional of TF and SDC2 (multi-omics screening approach) can increase the detection rate of advanced neoplasm by 17.4% and the detection rate of nonadvanced adenomas by 46.6%. The primary medical accessible and home self-test multi-omics CRC screening approach is a feasible and effective strategy for population-based CRC screening, and therefore could improve screening coverage at the primary medical institution in the rural and urban area. Major projects of special development funds for Shanghai Zhangjiang National Innovation Demonstration (ZJ2021-ZD-007).