AUTHOR=Liao Yan , Weng Junmei , Chen Lian , Hu Nan , Yuan Xun , Wang Jianhua , He Feng , Cai Yixin , Huang Qin , Wang Jianing , Huang Liu
TITLE=Comprehensive analysis of SLC43A2 on the tumor immune microenvironment and prognosis of liver hepatocellular carcinoma
JOURNAL=Frontiers in Genetics
VOLUME=13
YEAR=2022
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.911378
DOI=10.3389/fgene.2022.911378
ISSN=1664-8021
ABSTRACT=Background: 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.
Methods: The TCGA-LIHC dataset (n = 374) and the ICGC-LIRI-JP-LIHC (n = 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.
Results: 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 p < 0.001) and with increased infiltration of Tregs, macrophages and myeloid-derived suppressor cells (MDSC) (all p < 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.
Conclusion: 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.