Multiple omics integrative analysis identifies GARS1 as a novel prognostic and immunological biomarker: from pan-cancer to bladder cancer

Abstract

Glycyl-tRNA synthetase (GARS1) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan–Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.