Research has established that the overexpression of m5C methyltransferases, including NSUN2, NSUN4, and NSUN6, as well as m5C “readers” such as YBX1 and ALYREF, is strongly linked to tumor progression, poor prognosis, and treatment resistance across cancers like esophageal squamous cell carcinoma (ESCC), GC, HCC, CRC, and PDAC. This evidence concerns the gene ALYREF and hepatocellular carcinoma.