Identification of SLC1A5 as a Novel Candidate Oncogene for Glioma and Its Involvement in the LGG Immune Microenvironment

Abstract Background: Solute Carrier Family 1 Member 5 (SLC1A5), a member of the amino acid carrier system, is considered an oncogene in various tumors. Several targeted drugs targeting SLC1A5 are being developed. However, the molecular mechanisms of SLC1A5 in gliomas are not fully known. Methods: In this study, multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database were analyzed. Gene Set Enrichment Analysis (GSEA) was performed to identify biological functions and signaling pathways of SLC1A5. The correlation between SLC1A5 expression and immune infiltrates or gene signatures of immune cells was then determined using CIBERSORT and online analysis tools (TIMER, TSIDB). Finally, a reliable prognostic signature based on SLC1A5-related immunomodulators prognostic signature (SLC1A5-IPS) was established using the lasso-cox method. The model divided patients into low- and high-risk groups. The prognostic value of the risk scores was evaluated with univariate, multivariate, nomogram and receiver operating characteristic (ROC) curves.Results: It was found that high expression of SLC1A5 was associated with poor prognosis of glioma. Enrichment analysis indicated that SLC1A5 was regulated tumor immune response. Moreover, SLC1A5 was closely associated with immune cells infiltration and gene signatures of CD8 cells were positively correlated with SLC1A5 expression. Moreover, the developed SLC1A5-IPS risk model showed that the high-risk scores of SLC1A5-IPS accurately predicted poor prognosis of LGG. The constructed nomogram exhibited good prediction of the overall survival (OS) of LGG patients in all datasets. Finally, in vitro assays verified that SLC1A5 knockdown led to a loss of migration and proliferation ability of U87 and U251 cells. Conclusions: SLC1A5 regulates immune cells infiltration in glioma and promotes the proliferation and migration ability of glioma cells, thereby affecting the prognosis of patients. It therefore holds huge potential as a treatment target in glioma and provide a new direction for drug development.