Among the genes methylated in all four CRC samples, several well-characterized genes were observed, including PDPN, MFAP2, and RCC1. PDPN encodes a type I transmembrane sialomucin-like glycoprotein that plays a key role in tumor invasion, has been reported to be upregulated in cancer-associated fibroblasts (CAFs) in early-stage CRC (Tsukamoto et al., 2024). Here, RCC1 is linked to cancer.