Our group has recently developed multiple comprehensive integrative bioinformatics methodologies to identify new biomarkers involved in hypoxic solid tumor progression.15,40–42 Among the candidate tumor related new biomarkers, MrgprF, a MAS related GPR family member, was revealed to be downregulated in CM due to the hypermethylation in its promoter region, which could be reversed by 5-Azacytidine treatment, a well-known anti-cancer drug.43,44 Consistently, 5-Azacytidine has previously been shown to behave as an anti-neoplastic agent for B16 melanoma.45,46. Here, ALDH18A1 is linked to melanoma.