Transcriptome sequencing and single-cell sequencing analysis identify GARS1 as a potential prognostic and immunotherapeutic biomarker for multiple cancers, including bladder cancer

Jianqiang Nie; Taobin Liu; Taotao Mao; Hailang Yang; Wen Deng; Xiaoqiang Liu; Bin Fu

doi:10.3389/fimmu.2023.1169588

Transcriptome sequencing and single-cell sequencing analysis identify GARS1 as a potential prognostic and immunotherapeutic biomarker for multiple cancers, including bladder cancer

Front Immunol. 2023 Jun 19:14:1169588. doi: 10.3389/fimmu.2023.1169588. eCollection 2023.

Authors

Jianqiang Nie¹, Taobin Liu¹, Taotao Mao², Hailang Yang¹, Wen Deng¹, Xiaoqiang Liu^{1

3}, Bin Fu^{1

3}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
² Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
³ Jiangxi Institute of Urology, Nanchang, China.

Abstract

Background: Glycyl-tRNA synthetase 1 (GARS1) belongs to the aminoacyl-tRNA synthetase family, playing a crucial role in protein synthesis. Previous studies have reported a close association between GARS1 and various tumors. However, the role of GARS1 in human cancer prognosis and its impact on immunology remain largely unexplored.

Methods: In this study, we comprehensively analyzed GARS1 expression at the mRNA and protein levels, examined genetic alterations, and assessed its prognostic implications in pan-cancer, with a specific emphasis on the immune landscape. Furthermore, we investigated the functional enrichment of genes related to GARS1 and explored its biological functions using single-cell data. Finally, we conducted cellular experiments to validate the biological significance of GARS1 in bladder cancer cells.

Results: In general, GARS1 expression was significantly upregulated across multiple cancer types, and it demonstrated prognostic value in various cancers. Gene Set Enrichment Analysis (GSEA) revealed the association of GARS1 expression with multiple immune regulatory pathways. Moreover, GARS1 exhibited significant correlations with immune infiltrating cells (such as DC, CD8⁺T cells, Neutrophils, and Macrophages), immune checkpoint genes (CD274, CD276), and immune regulatory factors in tumors. Additionally, we observed that GARS1 could effectively predict the response to anti-PD-L1 therapy. Notably, Ifosfamide, auranofin, DMAPT, and A-1331852 emerged as potential therapeutic agents for GARS1-upregulated tumors. Our experimental findings strongly suggest that GARS1 promotes the proliferation and migration of bladder cancer cells.

Conclusion: GARS1 holds promise as a potential prognostic marker and therapeutic target for pan-cancer immunotherapy, offering valuable insights for the development of more precise and personalized approaches to tumor treatment in the future.

Keywords: GARS1; bladder cancer; immunotherapeutic; pan-cancer; prognosis biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

B7 Antigens
Biomarkers
Glycine-tRNA Ligase*
Humans
Prognosis
Transcriptome
Urinary Bladder Neoplasms* / genetics
Urinary Bladder Neoplasms* / therapy

Substances

Glycine-tRNA Ligase
Biomarkers
CD276 protein, human
B7 Antigens

Grants and funding

This study was supported by the National Natural Science Foundation of P.R. China (Grant Nos. 81560419, 81960512), and Project of Natural Science Foundation of Jiangxi Province (20202BABL206032).