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=Volume 13 - 2022

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=Abstract 
Background
Tumor cells overexpressed SLC43A2 to outcompete T cells for methionine, which resulted in T cell exhaustion. We explored the influence of SLC43A2 related IRG on the immune infiltrates' abundances and survival of LIHC patients.
Methods
The TCGA-LIHC dataset (n = 374) was used as testing cohort and the LIRI-JP dataset (n=231) as validation cohort. IRGs were obtained from the ImmPort. Statistical analyses were performed with R (V 4.0.5). Online databases such as GEPIA, GSCALite, The Kaplan Meier plotter, STRING, KEGG, TIMER2 and CMap were used for differential expression, immune infiltration, functional enrichment, survival and drug-induced gene perturbation analysis.
Results
Higher SLC43A2 expression was found in tumor tissues and significantly correlated with worse survival in LIHC (all P < 0.05). More CD4+ T cell, Tregs, Macrophage, MDC, and MDSC were infiltrated in LIHC patients with high SLC43A2 expression, but less naive CD8+ T cell, Endothelial cell, and Hematopoietic stem cell were. SLC43A2 was positively correlated with immune-depleted markers (all P < 0.001). Based on its related IRGs, we constructed and validated a prognostic risk score model. Arachidonic acid, SB-202190 and guanethidine were identified as possible immunomodulators for LIHC.
Conclusions
SLC43A2 governed suppressive immune cells infiltration to LIHC. A new risk score model based on SLC43A2 related IRGs could identify patients at higher risk in LIHC. Arachidonic acid, SB-202190 and guanethidine might act as immunomodulators for LIHC via interfering with SLC43A2 and need to be studied in the future.