Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma.

Tumor cells outcompete T cells for methionine via overexpressing SLC43A2, causing T cells exhaustion. We explored the influence of SLC43A2 on tumor immune microenvironment (TIME), immune-related genes (IRGs) and the prognosis of liver hepatocellular carcinoma (LIHC) patients. The TCGA-LIHC dataset ( = 374) and the ICGC-LIRI-JP-LIHC ( = 231) datasets were used as training and validation cohort, respectively. IRGs were obtained from ImmPort. Statistical analyses were performed using R (V 4.0.5). Online databases such as GEPIA, GSCALite, the Kaplan-Meier plotter, KEGG, TIMER2, and CMap were used for differential expression, immune infiltration, functional enrichment, survival, and drug-induced gene perturbation analysis. SLC43A2 expression was higher in LIHC, correlated with worse survival, but could not predict prognosis of LIHC separately (AUC = 0.467). SLC43A2 positively correlated with immune exhaustion markers (all < 0.001) and with increased infiltration of Tregs, macrophages and myeloid-derived suppressor cells (MDSC) (all < 0.05). SLC43A2 may regulate 120 IRGs. A prognostic risk score model was developed using the TCGA-LIHC cohort and validated by the ICGC-LIRI-JP cohort. Arachidonic acid, SB-202190 and guanethidine were identified as possible immunomodulators pharmacologically targeting SLC43A2 in LIHC. SLC43A2 may create suppressive tumor microenvironment and regulate related IRGs, thus affecting the prognosis of LIHC. Arachidonic acid, SB-202190, and guanethidine may be worthy of further study as immunomodulators on SLC43A2.