These findings are in light with previous literature [50], support the significance of MTHFD2 as a potential therapeutic target in ESCA and suggest that targeting MTHFD2 could be a promising approach to inhibit tumor growth and progression, as well as a link between the identified metabolic subtypes and their associated molecular mechanisms, adding to the overall understanding of ESCA heterogeneity and its clinical implications. This evidence concerns the gene MTHFD2 and neoplasm.