TMEFF2 and metastatic neoplasm: Moreover, other cfDNA biomarkers with abnormal DNA methylation, including genes of TPEF/HPP1, ALX4, TMEFF2, NGFR, NEUROG1, FRP2, APC, MLH1, RUNX3, and CDKN2A/P16h, have been indicated to be extremely sensitive and specific in CRC patients, along with methylated HLTF, as powerful prognostic biomarkers associated with tumor stage and size, metastatic disease, and recurrence of illness.