Study on HOXBs of Clear Cell Renal Cell Carcinoma and Detection of New Molecular Target

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.

Figure 1

Comparison of the mRNA level of HOXBs in different tumor tissues by the ONCOMINE database. Among them, red represents high expression and blue represents low expression.

Figure 2

Expression of HOXBs in renal carcinoma (GEPIA). (a) The differential expression of HOXBs between normal kidney and KIRC, KIRP, and KICH using the GEPIA database. (b–k) Scatterplot of the differential expression of HOXBs between normal kidney and KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma), and KICH (kidney chromophobe) using the GEPIA database (histogram). GEPIA, expression profile analysis.

Figure 3

The differential expression of HOXBs in different stages of renal cell carcinoma using GEPIA database (a–j).

Figure 4

Using Human Protein Atlas to investigate the relationship between the mRNA of HOXBs and the prognosis (a–i). The expression of HOXB1 was too low to be analyzed.

Figure 5

(a) Using the STRING website to analyze the interaction between HOXBs. (b–d) Using the GSCALite website to analyze the CNV of HOXBs. (e, g) Analyzing the DNA methylation of HOXBs. (f, i) Analyzing the potential pathway of HOXBs. (h) Analyzing the potential drug target of HOXBs.

Figure 6

The coexpression of HOXBs was analyzed using the cBioPortal online tool and visualized using an online tool (a, b).

Figure 7

(a) Constructing a network of HOXB factors and their adjacent gene alteration through the STRING website. (b–d) Using the Gene Ontology analysis by DAVID tools, we predicted the functions of HOXBs and genes associated with HOXBs alterations and then visualized them through R language. (e) Through the analysis of KEGG and PANTHER using DAVID tools, predict the functions of HOXBs and genes associated with HOXB alterations and visualize them using the R language.

Figure 8

The Wnt pathway. The red mark indicates enrichment through the analysis of the KEGG pathway of the functions of HOXBs and genes associated with HOXBs alterations on the DAVID website.

Figure 9

Through the cBioPortal website, we investigated the coexpression of the Wnt pathway classical protein with genes that have significance in expression and survival (a–d).