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

Sep 21, 2026

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Glycyl-tRNA synthetase (GARS1) shows differential expression across cancers. Multiple omics integrative pan-cancer analysis combined with experimental validation evaluates its diagnostic and prognostic value using Kaplan–Meier, ROC testing, and multiple databases. PPI, GO, KEGG, methylation modeling, and a genetic mutation atlas define a GARS1 relative reaction network. In bladder urothelial carcinoma, regression and nomogram models connect GARS1 with immune markers, immune cells, and five MMR genes, highlighting links to M2 macrophages, TAMs, Th1, and T-cell exhaustion. In vitro assays confirm GARS1 promotes proliferation and metastasis while inhibiting apoptosis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

GARS1 across cancers

Diagnostic and prognostic assessment

GARS1 network and pathway analysis

Focus on bladder urothelial carcinoma (BLCA)

Regression and nomogram modeling

Immune correlation and immune microenvironment

Experimental validation in vitro

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Multiple omics integrative analysis identifies GARS1 as a novel prognostic and immunological biomarker: from pan‑cancer to bladder cancer Weihui Liu1,2,6, Chengcheng Wei3,4,6, Qingliu He2, Zhaohui Chen3, Wei Zhuang2, Yihong Guo2* & Xueyi Xue5* 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. Keywords GARS1, Pan-cancer, Bladder cancer, Multiple omics, Immune infiltration Cancer remains the leading cause of death worldwide, highlighting the urgent need for prognostic biomarkers to guide treatment decisions1. Platinum-based chemotherapy is the standard regimen for bladder cancer; however, approximately 50% of patients are not suitable candidates due to various issues, including renal insufficiency, complications, age, and poor physical condition2. Immune checkpoint inhibitors (ICIs) have been approved asa first-line treatment for PD-L1-positive metastatic bladder urothelial cancer (mBLCA) in patients who cannot tolerate cisplatin, as well as for use as a second-line therapy following progression after cisplatin treatment3. Despite bladder cancer being a highly immunogenic tumor, only a subset of mBLCA patients benefit from ICI therapy. The underlying mechanisms for this variability in response to ICI treatment remain poorly understood4. Additionally, immune-related adverse events, such as liver function impairment, can adversely affect treatment 1Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. 2Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China. 3Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China. 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 404100, China. 5Department of Urology, Urology Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China. 6These authors contributed equally: Weihui Liu and Chengcheng Wei.* email: [hotniu@fmu.edu.cn](hotniu@fmu.edu.cn); [cmd15205014314@163.com](cmd15205014314@163.com) [www. nature.com/sci

FAQs

How was the diagnostic and prognostic value of GARS1 assessed across cancers?

GARS1 expression patterns were evaluated using a multiple omics integrative pan-cancer analysis with Kaplan–Meier and ROC, supported by multiple databases.

What analyses were used to explore the GARS1-related reaction network?

The study identified a GARS1 relative reaction network using PPI, GO, KEGG, methylation models, and a genetic mutation atlas.

What is the relationship between GARS1 and the immune microenvironment in BLCA?

In BLCA, GARS1 expression correlates with immune cell infiltration and immune marker patterns, including M2 macrophages and TAMs, and relates to T-cell exhaustion and specific MMR genes.

Sep 21, 2026

Uploaded by Ezra