To our knowledge, this is the first report on the use of methylated SDC2, TFPI2, WIF1, and NDRG4 genes for early detection of GCC, which not only retains the advantages of simple and non-invasive characteristics similar to FOBT, but also higher sensitivity and specificity to the screening or auxiliary diagnosis of a high-risk population with GCC. Here, TFPI2 is linked to goblet cell carcinoma.