High-risk genes in the model, including GPX3, AKR1C4, SPHK1and ADCY5, have been reported to promote hypermethylation, rare mutations, cancer progression, poor prognosis, and the developmental process of malignant cells in CRC patient samples or cell lines (Gylfe et al., 2013; Kawamori et al., 2009; Liang et al., 2013; Pan et al., 2019; Zhou et al., 2019). Here, AKR1C4 is linked to cancer.