Clinical utility of stool-based SDC2 methylation test for the detection and screening of colorectal cancer in a Chinese population.

Abstract

3525 Background: In 2020, colorectal cancer (CRC) ranks second in incidence and third in mortality among all types of cancers in China based on data from GLOBOCAN. Moreover, the rates of incidence and mortality have been continuously rising over the past several decades. In addition to conventional methods for detection and screening of CRC such as gFOBT, FIT, and colonoscopy, a stool-based methylation test of human SDC2 gene was recently approved by National Medical Product Association (NMPA) of China. We hereby report the performance of this newly approved test in a hospital-based cohort of more than 10,000 patients in the real world of daily clinical practice. Methods: The methylation target, human SDC2 gene, was extracted from stool and purified via sequence-specific capture technology. The isolated DNA was further treated with bisulfite before it was subsequently amplified by quantitative methylation-specific polymerase chain reaction (qMSP) to analyze the fecal level of SDC2 methylation. Subjects were further examined by colonoscopy or CT imaging. Pathological examination would also be performed in cases deemed necessary. Results: A total of 11,284 individuals were tested using the novel SDC2 methylation test. Among them, 858 and 10,426 were tested positive and negative, respectively. Follow-up visits, treatment, and medical information were complete for 429 positive and 780 negative patients who were included in this final analysis. Positive predictive value (PPV) of CRC and adenomas was 36.4% (156/429) and 24.5% (105/429), respectively. Stratified analysis implies that SDC2 methylation level in CRC was significantly higher than those in adenoma and normal groups. In CRC, no significant correlation was observed between SDC2 methylation and clinicopathological features including gender and grade of dysplasia. In < 65 and ≥ 65 age groups, the CRC detection rate in males was higher than that in females―almost two times higher in ≥ 65 age group. Conclusions: The stool-based SDC2 methylation test demonstrated high accuracy in the detection of CRC and advanced adenomas. It is a sensitive and valid modality expected to play a significant role to aid diagnosis and screening of CRC and precancerous lesions in order to reduce the morbidity and mortality of this malignant disease.