Solute carrier family 12 member 8 (SLC12A8) is a potential biomarker and related to tumor immune cell infiltration in bladder cancer

ABSTRACT

The solute carrier family has been reported to play critical roles in the progression of several cancers; however, the relationship between solute carrier family 12 member 8 (SLC12A8) and bladder cancer (BC) has not been clearly confirmed. This study explores the prognostic value of SLC12A8 for BC and its correlation with immune cell infiltration. We found that the expression of SLC12A8 mRNA was significantly overexpressed in BC tissues compared with noncancerous tissues in multiple public databases, and the result was validated using real-time PCR and immunohistochemistry (IHC). The Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of SLC12A8 for BC. The high expression of SLC12A8 led to a shorter overall survival time and was an unfavorable prognostic biomarker for BC. The mechanisms of SLC12A8 promoting tumorigenesis were investigated by Gene Set Enrichment Analysis (GSEA). Moreover, the correlations of SLC12A8 expression with the tumor-infiltrating immune cells (TICs) in BC were explored using TIMER 2.0 and CIBERSORT. SLC12A8 was associated with CD4+ T cells, dendritic cells, neutrophils, and macrophages infiltration. The expression of SLC12A8 was positively correlated with crucial immune checkpoint molecules. In conclusion, SLC12A8 might be an unfavorable prognostic biomarker in BC related to tumor immune cell infiltration.

KEYWORDS:

• SLC12A8
• bladder cancer
• tcga
• cibersort
• timer2.0
• immune infiltration
• immune checkpoint inhibitor

Acknowledgements

We thank the Laboratory of Rescue Center of Severe Wound and Trauma PLA and the Department of Oncology of General Hospital of Theater Command for providing the research platform for this study.

Highlights

(1) Bioinformatics analysis and clinical tissue validation were combined to analyze the gene expression of SLC12A8 in BC comprehensively.

(2) The correlation between SLC12A8 and tumor immune cell infiltration was explored.

(3) The prognostic value of SLC12A8 was evaluated, and its correlation with immune checkpoints was analyzed.

Abbreviations

Solute carrier family 12 member 8 (SLC12A8)

Bladder cancer (BC)

Gene Set Enrichment Analysis (GSEA)

Tumor-infiltrating immune cells (TICs)

Multi Experiment Matrix (MEM)

Programmed cell death protein 1 (PD-1)

Programmed death-ligand 1 (PD-L1)

Cytotoxic T-lymphocyte antigen-4 (CTLA-4)

Lymphocyte activation gene 3 protein (LAG3)

T cells immunoglobulin domain mucin domain protein-3 (TIM3)

T cell immunoglobulin and ITIM domain protein (TIGIT)

Molecular Signatures Database (MsigDB)

Hazard ratio (HR)

Gene Ontology (GO)

Kyoto Encyclopedia of Genes and Genomes (KEGG)Area under the curve (AUC)Hazard ratio (HR)

Receiver operating characteristic (ROC)

Extracellular matrix (ECM)

Immune checkpoint inhibitors (ICIs)

Ethics approval and consent to participate

The ethics committee approved the study of the General Hospital of Northern Theater Command (Shenyang, Liaoning, P.R. China), and the IRB approval number is Y (2021) 039.

Consent for publication

All the authors agree to publish in this journal.

Disclosure statement

We declare that we have no competing interests and personal relationships with other people or organizations.

Author’s contributions

Qian Zhang, Cheng Du, Yunen Liu conceived and designed the experiments. Qian Zhang, Xiuyun Shi, and Ying Liu performed the experiments. Qian Zhang, Lin Shi, and Peng Chen processed the data. Peifang Cong, Shun Mao, and Cangci Tong prepared the figures and tables Qian Zhang drafted the work. Mingxiao Hou revised it critically for important content.

Availability of data and materials

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by the Liaoning Provincial Natural Science Foundation (the clinical and translational research of cold plasma combined with targeted SLC12A8 for local therapy of BC, 2020-MS-039, Cheng Du).