SMYD3 and colorectal carcinoma: Interestingly, we found that 5 out of 7 SMYD3-overexpressing CRC patients belong to the consensus molecular subtype 4 (CMS4), which is considered the worst CMS because it is characterized by a mesenchymal phenotype with gene signatures consistent with an activated stroma.40 Moreover, CMS4 CRCs are often diagnosed at advanced stages and have a poor prognosis, with the worst 5-year overall survival (62%) and relapse-free survival (60%) of any molecular subtype.40 These data suggest that patients with SMYD3-overexpressing CRC have a more aggressive phenotype (Fig. 4a).