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Published on: February 8, 2020
Study on HOXBs of Clear Cell Renal Cell Carcinoma and Detection of New Molecular Target
Guangzhen Wu1, Xiaowei Li1, Yuanxin Liu1
1Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Abstract:
Our study examined the transcriptional and survival data of HOXBs in patients with clear cell renal cell carcinoma (ccRCC) from the ONCOMINE database, Human Protein Atlas, and STRING website. We discovered that the expression levels of HOXB3/5/6/8/9 were significantly lower in ccRCC than in normal nephritic tissues. In ccRCC, patients with a high expression of HOXB2/5/6/7/8/9 mRNA have a higher overall survival (OS) than patients with low expression. Further analysis by the GSCALite website revealed that the methylation of HOXB3/5/6/8 in ccRCC was significantly negatively correlated to gene expression, while HOXB5/9 was positively correlated to the CCT036477 drug target. As DNA abnormal methylation is one of the mechanisms of tumorigenesis, we hypothesized that HOXB5/6/8/9 are potential therapeutic targets for patients with ccRCC. We analyzed the function of enrichment data of HOXBs in patients with ccRCC from the Kyoto Encyclopedia of Genes and Genomes pathway enrichment and the PANTHER pathway. The results of the analysis show that the function of HOXBs might be associated with the Wnt pathway and that HOXB5/6/8/9 was coexpressed with multiple Wnt pathway classical genes and proteins, such as MYC, CTNNB, Cyclin D1 (CCND1), and tumor protein P53 (TP53), which further confirms that HOXBs inhibit the growth of renal carcinoma cells through the Wnt signaling pathway. In conclusion, our analysis of the family of HOXBs and their molecular mechanism may provide a theoretical basis for further research.
Insights
HOXB gene expression is reduced in clear cell renal cell carcinoma (ccRCC), but higher HOXB levels correlate with better patient survival. HOXB5/6/8/9 may be therapeutic targets, potentially acting through the Wnt signaling pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a significant health concern.
- The role of HOXB genes in ccRCC pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the expression patterns and prognostic significance of HOXB genes in ccRCC.
- To explore the potential therapeutic targeting of HOXB genes in ccRCC.
Main Methods:
- Analysis of transcriptional and survival data from public databases (ONCOMINE, Human Protein Atlas, STRING).
- Gene expression, methylation, and pathway enrichment analyses (GSCALite, KEGG, PANTHER).
Main Results:
- HOXB3/5/6/8/9 expression is significantly lower in ccRCC compared to normal tissues.
- Higher expression of HOXB2/5/6/7/8/9 mRNA correlates with improved overall survival in ccRCC patients.
- HOXB5/6/8/9 methylation is linked to gene expression and drug targets, suggesting a role in tumorigenesis.
- HOXBs are associated with the Wnt signaling pathway and coexpressed with key pathway genes (MYC, CTNNB, CCND1, TP53).
Conclusions:
- HOXB genes, particularly HOXB5/6/8/9, show altered expression and prognostic value in ccRCC.
- HOXB genes may serve as potential therapeutic targets for ccRCC, potentially through modulation of the Wnt pathway.
- Further research into HOXB family function and molecular mechanisms is warranted for ccRCC treatment strategies.
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