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The Cartilage Oligomeric Matrix Protein (COMP) Gene Is Associated with High-Grade Bladder Cancer and Promotes Bladder Cancer Cell Proliferation

ABSTRACT: Bladder cancer (BLCA) is a globally prevalent malignancy that poses a severe threat to patient health. Accurate high/low-grade classification of BLCA is critical for tailoring effective treatment strategies. This study integrated eight single-cell RNA sequencing (scRNA-seq) datasets and bulk RNA sequencing test from bladder tissues in our hospital, performing cell subpopulation annotation, differential gene expression analysis, and pathway enrichment analysis. Focusing on Cartilage Oligomeric Matrix Protein (COMP), we evaluated drug sensitivities and validated its functional role in BLCA using 5637 cell lines. Single-cell clustering identified distinct gene expression profiles between high/low-grade bladder epithelial cells, with the unfolded protein response pathway being most significantly enriched. Integrative analysis revealed COMP as a prognostic marker, positively correlated with 16 potential therapeutic drugs. In vitro experiments confirmed that COMP promotes BLCA cell proliferation. Our findings highlight COMP as an oncogenic driver in BLCA and provide drug targets for clinical translation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311318 | GEO | 2025/11/28

REPOSITORIES: GEO

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			Action	DRS
		Other
	GSE311318_proceed_files_gene_TPM.csv.gz	Csv
	GSE311318_proceed_files_gene_count.csv.gz	Csv

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Project description:Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response. Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor–ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing. Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor–ligand pairs. Conclusions: Patients with BLCA with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA. Keywords: bladder cancer, TP53, immunosuppression, tumor microenvironment

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The Cartilage Oligomeric Matrix Protein (COMP) Gene Is Associated with High-Grade Bladder Cancer and Promotes Bladder Cancer Cell Proliferation

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