AKR1B1 and hepatocellular carcinoma: Among these clusters, iCluster_3 exhibited marked chromosomal instability, increased TP53 mutation rates, and widespread hypomethylation at multiple CpG loci.43 Survival analysis of TCGA data revealed that patients in this group with high AKR1B1 expression had significantly shorter survival times, highlighting the robust correlation between elevated AKR1B1 expression and unfavorable outcomes in HCC (Fig. 5c).