DNA methylation analysis of SCD2, SEPT9 and VIM genes for the early detection of colorectal cancer in fecal DNA

Background Colorectal cancer (CRC) is one of the most common cancers worldwide, with increasing mortality and morbidity. DNA methylation sites may serve as a new genes signature for early diagnosis. The search for representative DNA methylation sites is urgently needed. This study aimed to systematically identify a methylation gene panel for CRC using tissue and fecal samples. Methods A total of 181 fecal and 50 tumor tissue samples were collected. They were obtained from 83 CRC patients and 98 healthy subjects. These samples were evaluated for DNA methylation analyzing of 9 target genes by quantitative bisulfite next-generation sequencing. We employed the Rank-sum test to screen the CRC-specific methylation sites in the tissue and stool cohort. Subsequently, a data model was constructed and validated using the dedicated validation dataset. Results For all the selected gene sites, CRC tissue samples showed significantly higher methylation rates than fecal and negative controls samples. Methylation rates of tissue and preoperative fecal samples showed the same high and low rates at the same sites. After screening, a panel of 29 locus in the genes SCD2, SEPT9, and VIM proved a reliable biomarker for CRC detection in fecal samples. Logistic regression models were then constructed and validated using this panel. Sensitivity of the model is 91.43% (95% CI=[89.69, 93.17]) and specificity is 100% (95% CI=[100,100]). This confirms the validity of the screened panel to effectively detect CRC via feces. Conclusions Our study identifies a set of key methylation sites for the detection of CRC from fecal samples, highlighting the significance of using tissue and fecal samples to accurately assess DNA methylation levels to screen for methylation sites and developing an effective model for early detection of CRC.