Based on the methylation bioinformatics data and experimental validation, a set of cancer-specific genes and/or lncRNAs were selected that differentiate each cancer type from other cancers and NATs: RNF135 and EFNB2 for HCC, RNF125, ABLIM1 and HOXC4 for CCA, OSMR and LIFR-AS1 for CRC and CRC liver metastases (CRLM) and PROX1-AS1 for PDAC and PCLM. The gene discussed is RNF135; the disease is hepatocellular carcinoma.