HNF4A and colorectal carcinoma: Interestingly, CES1 was alternatively upregulated by prognostically unfavorable amplifications of the gene encoding its transcriptional regulator, Hepatocyte nuclear factor 4 alpha (HNF4A), in the canonical CMS2 subtype,16 underscoring how different oncogenic pathways converge on CES1 to drive CRC (Figure 1).