The present study prospectively explores the value of quantitative SEPT9 and SHOX2 methylation levels in ccfDNA for disease staging of CRC patients in addition to current TNM staging system and along with the established serum biomarkers carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA 19–9). This evidence concerns the gene SHOX2 and colorectal carcinoma.