Fig. 5

Associations of AKR1B1 expression with HCC patient prognosis and primary drug resistance. a The HCC cohort was divided into three clinical therapy subcohorts: no chemotherapy (NC), partial response (PR), and disease progression (DP). Clinical parameters are indicated in the heatmap. MVI: microvascular invasion; T stage: tumor stage; TACE: transcatheter arterial chemoembolization; HAIC: hepatic arterial infusion chemotherapy. b Comparison of AKR1B1 expression levels in tumor tissues among HCC patients in the NC, PR, and DP subcohorts. c OS rate of patients in the TCGA HCC iCluster_3 cohort in relation to AKR1B1 expression levels. Testing methods: Comparison of survival differences between the two groups: log-rank test; calculation of the hazard ratio (HR): Cox regression model. d Heatmap illustrating drug sensitivity in parental cells following AKR1B1 overexpression. e Schematic representation of CM extraction from drug-resistant cells and its application to parental cells. Schematic figures were generated with BioRender (https://app.biorender.com/). f Live/dead fluorescent probe analysis of drug resistance transfer and cell mortality in parental 3D microtissues cultured with conditioned medium from drug-resistant cells. Scale bar = 50 μm. Testing method: Unpaired Student’s t-test. g Cell tracing and IF analysis of AKR1B1 transfer from drug-resistant cells to parental cells. Cell tracing (green): drug-resistant cells; AKR1B1 (red); nuclei (blue). Scale bar = 20 μm. h WB analysis of AKR1B1 expression in various HCC cell lines and drug-resistant cells via statistical analysis. i Drug sensitivity evaluation was performed on the basis of IC₅₀ values to assess drug resistance transfer between multiple HCC cell lines via CM. Testing method: Unpaired Student’s t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001