Bioinformatics Prediction and in vivo Verification Identify SLC7A5 as Immune Infiltration Related Biomarker in Breast Cancer

Abstract

Purpose Solute carrier family 7, member 5 (SLC7A5) is reportedly a key gene in various tumors. However, the relationship between SLC7A5 and immune cell infiltration in breast cancer remains elusive. In this study, we investigated the expression levels and clinical value of SLC7A5 using the R package in breast cancer through the TCGA database. Methods Public transcript data and clinical information of patients were downloaded from the TCGA database. Prognosis analysis was performed to explore the clinical value of SLC7A5 as well as drug sensitivity prediction and Gene Set Enrichment Analysis (GSEA). We also explored the correlations between SLC7A5 and immune infiltration as well as immune markers. Results We observed that high SLC7A5 expression levels were related to poor survival. Our GSEA demonstrated that G protein-coupled receptor-ligand binding, interleukin signaling, neutrophil degranulation, amino acid and derivative metabolism, and Rho GTPase signaling were differentially enriched in the SLC7A5 high-expression phenotype. Patients in the low SLC7A5 expression group showed sensitivity to paclitaxel and doxorubicin. Conclusion SLC7A5 could serve as a biomarker for breast cancer prognosis.

Amino acid metabolism in health and disease

“… 271 Another bioinformatics analysis for breast cancer reached a similar conclusion. 272 In addition, BCAT isoenzymes may serve as markers of tumor TME status. In non-malignant T cells, such as activated CD4 + T cells and CTL cells, BCAT c accounts for 50% of the total BCAT expression level, whereas this proportion is upregulated to 60% in T-cell lymphomas.…”

“…Subsets with different preferences for BCAA metabolism have also been found in breast cancer, and further studies are needed to determine whether this is due to differences in tumor cells or the involvement of other cells in the microenvironment. 55,59 BCAA metabolism is equally important for the function of proinflammatory CD4 + and CD8 + T cells and immunosuppressive regulatory Treg cells, 41,[265][266][267][268][269][270][271][272] which plays key role in metabolic diseases, liver and kidney diseases. 10,11,[65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84]345,346 Currently, drugs targeting BCAA uptakedependent amino acid transporter LAT1 metabolic enzymes BCAT and BCKDK are in trials.…”

Amino acids and their roles in tumor immunotherapy of breast cancer

“…61 A recent study showed that SLC7A5 was an immune infiltration-related biomarker and breast cancer patients with high SLC7A5 expression were insensitive to paclitaxel and doxorubicin and had poor prognoses. 62…”

“…Furthermore, SLC7A5 expression is positively associated with tumor size, histological grade, tumor infiltrating lymphocytes (TILs), and programmed death ligand 1 (PD‐L1) while negatively associated with ER and progesterone receptor (PR) in breast cancer 61 . A recent study showed that SLC7A5 was an immune infiltration‐related biomarker and breast cancer patients with high SLC7A5 expression were insensitive to paclitaxel and doxorubicin and had poor prognoses 62 …”

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay

“…High cellular leucine concentration activates the mTOR pathway and promotes cell proliferation [ 20 ]. SLC7A5 is known to be highly expressed in many cancers [ 21 , 22 ]. In KRAS-mutant colorectal cancer cells, SLC7A5 maintained intracellular amino acid level and activated mTOR pathway, which finally supported cell proliferation [ 23 ]; in small cell lung cancer, increased SLC7A5 promoted cell growth [ 24 ].…”