Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, 362000, China.
Sci Rep. 2024 Aug 16;14(1):19025. doi: 10.1038/s41598-024-70041-1.
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.
甘氨酰-tRNA 合成酶(GARS1)在各种癌症中表达不同。在这项研究中,通过多组学整合泛癌分析和实验验证,综合评估了 GARS1 在各种癌症的诊断和预后中的价值。通过 Kaplan-Meier、ROC 和多个数据库,我们探讨了 GARS1 在癌症中的表达和预后及诊断模式。在 PPI、GO、KEGG、甲基化模型和遗传突变图谱中鉴定了 GARS1 的相对反应网络。通过回归和列线图模型进一步研究了 GARS1 在膀胱癌(BLCA)中的价值。我们进一步分析了 GARS1 与 BLCA 中免疫标志物和细胞的相关性。最后,通过体外实验验证了 GARS1 在 BLCA 中的致癌功能。我们发现 GARS1 在各种癌症中表达较高,尤其是在 BLCA 中。GARS1 的表达与不良生存相关,在大多数肿瘤类型中具有较高的诊断价值。GARS1 与 tRNA 相关途径显著相关,其突变位点主要位于 tRNA 合成酶上。此外,GARS1 的上调与免疫细胞浸润和五个关键 MMR 基因相关。M2 巨噬细胞、TAMs、Th1 和 T 细胞耗竭以及与 GARS1 表达相关的标记集表明 BLCA 中存在特定的免疫浸润。最后,体外实验验证了 GARS1 表达促进 BLCA 细胞增殖、转移和抑制凋亡。总之,通过多组学整合泛癌分析,GARS1 可以成为一种新的预后和免疫生物标志物。GARS1 在 BLCA 中的表达与特定的免疫浸润呈正相关,表明 GARS1 可能与肿瘤免疫微环境有关。