In summary, the DNA methylation profiles of NASH-related HCCs may determine the clinicopathological heterogeneity of tumors through alterations in the expression of tumor-related genes, such as SPHK1, INHBA, LTB and PDE3B. Participation of the DNA methylation status of these genes in determining the tumor phenotype may be specific to NASH-related HCCs. Here, SPHK1 is linked to metabolic dysfunction-associated steatohepatitis.