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2000
Volume 28, Issue 13
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Current evidence highlights clear cell renal carcinoma (ccRCC) as the most prevalent form of kidney cancer despite ongoing challenges in treating advanced-stage disease. Integrin subunit beta 3 (ITGB3) has recently emerged as a critical player in tumorigenesis, prompting our investigation into its role in ccRCC. This study aimed to elucidate the mechanisms responsible for ITGB3 downregulation and evaluate its clinical significance, particularly regarding its impact on the immune landscape within ccRCC.

Methods

We first conducted analyses utilizing data from both TCGA and GEO datasets to explore expression in ccRCC tissues. Subsequently, we evaluated the association between expression levels and patient prognosis and pathological staging. Pathway and functional enrichment analyses were performed to assess correlations between and immune and methylation-related pathways. Additionally, we examined the relationship between ITGB3 transcriptional expression and DNA hypermethylation. A prognostic risk model was developed using LASSO-based analysis on selected ITGB3-associated DNA methylation probes. Immunohistochemistry (IHC) analysis, alongside TIMER and ssGSEA results, was utilized to investigate expression and its association with immune cell infiltration.

Results

Our analyses revealed significant downregulation of ITGB3 mRNA expression in ccRCC tissues compared to other members of the ITGB family, consistent across TCGA and GEO datasets. Higher expression correlated with improved prognosis and lower pathological stage in ccRCC patients. Pathway and functional enrichment analyses demonstrated positive correlations between and immune and methylation-related pathways, while transcriptional expression showed a negative correlation with DNA hypermethylation. The established prognostic risk model identified a high-risk group with poorer survival probabilities than the low-risk group. Immunohistochemical quantification revealed a positive correlation between CD4+ and CD8+ immune cell infiltration and expression.

Conclusion

Overall, our study provides compelling evidence supporting the significant role of ITGB3 in ccRCC immunity. The downregulation of , coupled with its association with better prognosis and immune activation, suggests its potential as a therapeutic target and prognostic marker for this patient population.

© 2025 Bentham Science Publishers
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/content/journals/cchts/10.2174/0113862073311689240730112355
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ITGB3 is a Novel Prognostic Biomarker and Correlates with Aberrant Methylation and Tumor Immunity in Clear Cell Renal Cell Carcinoma
Comb Chem High Throughput Screen 28, 2233 (2025); https://doi.org/10.2174/0113862073311689240730112355
/content/journals/cchts/10.2174/0113862073311689240730112355
/content/journals/cchts/10.2174/0113862073311689240730112355
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  • Article Type:     Research Article
Keyword(s): ccRCC; DNA methylation; immune cells; ITGB3; risk model

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