A novel signature constructed by differential genes of muscle-invasive and non-muscle-invasive bladder cancer for the prediction of prognosis in bladder cancer.

Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE

Original Publication: [Lausanne : Frontiers Research Foundation]

Non-Muscle Invasive Bladder Neoplasms* ; Urinary Bladder Neoplasms*/genetics; Humans ; Muscles ; Prognosis ; Urinary Bladder ; Calgranulin B

Background: Bladder cancer (BCa) is a malignant tumor that usually forms cancer cells in the inner lining of the bladder. Hundreds of thousands of people worldwide have BCa diagnosed each year. The purpose of this study was to construct a prognostic model by differential expression of genes between muscular and non-muscular invasive BCa, and to investigate the prognosis of BCa patients.
Methods: The data of BCa patients was sourced from the GEO and TCGA database. Single-cell sequencing data was obtained from three patients in the GSE135337 database, and microarray data for verification was obtained from GSE32894. Univariate, Lasso and multivariate cox regression analyses were performed to construct the prognostic model. The prognostic features, immune features and drug sensitivity of the model were further evaluated. Single-cell data and microarray data were used to validate the differential expression of model genes between muscle-invasive and non-muscle-invasive BCa. The invasion and migration of BCa cells were evaluated using the transwell assay and wound-healing assay. The cell proliferation capacity was simultaneously evaluated using Colony formation experiments. The protein expression of the specific gene was detected by western blot analysis.
Results: We identified 183 differentially expressed muscle-invasive-related differential genes (MIRDGs), among which four were selected to establish a prognostic model. Based on our signature, patients in different groups displayed varying levels of immune infiltration and immunotherapy profiles. Single-cell sequencing data and microarray data confirmed that four invasion-related genes were expressed at higher levels in muscle-invasive BCa. Given the critical role of S100A9 in the progression of BCa, we performed further analysis. The results showed that protein expression of S100A9 was high in muscle-invasive BCa, and S100A9 knockdown could inhibit the proliferation, migration and invasion of BCa.
Conclusion: These findings demonstrated that the prognostic model for BCa patients was reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of BCa patients in the future. S100A9 may become a better prognostic marker and potential therapeutic target to further guide clinical treatment decisions.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Wang, Zhang, Jiang, Xu, Chen, Li, Wang, Le and Zhang.)

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Keywords: biomarker; bladder cancer; immune microenvironment; muscle-invasive; prognostic signature

0 (Calgranulin B)

Date Created: 20230911 Date Completed: 20230912 Latest Revision: 20230915

20230915

PMC10483405

10.3389/fimmu.2023.1187286

37691944