Potential Impact Of GLS And GOT2 On Tumor Immunity In Breast Cancer

Background:glutaminase 1(GLS)and mitochondrial aspartate transaminase(GOT2)are regarded as the key factors of glutamine metabolic.Tumor cells can be expressed with Immune checkpoint proteins,which can undermine immune response and attribute to tumor survival.Here we investigate whether the glutamine metabolic factors GLS/GOT2 influence the tumour microenvironment of breast invasive carcinoma(BRCA),and can it be more responsive to cytotoxic T-lymphocyte antigen-4(CTLA4)blockade.Methods:Expression of GLS and GOT2 was investigated across The Cancer Genome Atlas(TCGA)and gene expression omnibus(GEO)validated in our study.Patients with BRCA were divided into two clusters using consensus clustering based on the expression of GLS and GOT2.We then compared their clinical characteristics.Immune infiltration analyses were conducted using ESTIMATE,CIBERSORT,and single-sample gene set enrichment analysis(ss GSEA).In addition,we evaluated the expression of the targets of immune checkpoint inhibitors(ICIs).Weighted gene co-expression network analysis(WGCNA)was used to identify the genes related to both GLS/GOT2 expression and immunity.GSE25066 was utilized for external validation of immunological features between the two clusters.We also used quantitative polymerase chain reaction(Q-PCR)to validate the expression of GLS and GOT2 in breast cancer and paracancer tissues,as well as the expression of hub genes between different cluster patients.ResultsCluster 2 had higher expression of GLS and lesser so of GOT2,whereas Cluster 1had just the reverse.Cluster 1 had a higher T stage and age than Cluster 2.The latter had stronger immune infiltration,higher expression of targets of ICIs than Cluster 1.Moreover,WGCNA revealed 12 genes(BACH2、CIS、CELF2、IL18R1、PIWIL4、RUBCNL、PLCG2、RUNX3、LYN、TAGAP、UBASH3B、DAPK1),which is related to both the expression of GLS/GOT2 and immune scores.In addition,the 12 genes which are strongly associated with immune checkpoints CTLA4,and their expression in patients of different clusters was consistent with CTLA4.Conclusions:Breast cancer is classified into two types according to the transcriptome information of GLS and GOT2.One classification,which has higher expression of GLS and lower expression of GOT2 is related to CTLA4,which may benefit from immune checkpoint inhibitors of CTLA4.Figure [one] Reference [twelve]...