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Integrated bioinformatics analysis to identify the key gene associated with metastatic clear cell renal cell
Shiqi Miao1,2, Jing Song3, Qingyuan Liu4
1Department of Bioinformatics, The Basic Medical School of Chongqing Medical University, Chongqing, 400016, China.
Abstract:
Metastasis of clear cell renal cell carcinoma (ccRCC) is a leading cause of death. The purpose of this research was to investigate the key gene in ccRCC tumor metastasis. Three microarray datasets (GSE22541, GSE85258, and GSE105261), which included primary and metastatic ccRCC tissues, were obtained from the Gene Expression Omnibus (GEO) database. Expression profiling and clinical data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) dataset. A total of 20 overlapping differentially expressed genes (DEGs) were identified using the R limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DEGs were mainly enriched in tumor metastasis-related pathways. Gene expression analysis and survival analysis in the GEPIA2 database further identified the key gene HSD11B2. qRT-PCR result manifested that HSD11B2 level was significantly down-regulated in ccRCC tissues compared with adjacent normal tissues. ROC analysis showed that HSD11B2 exhibited good diagnostic efficiency for metastatic and non-metastatic ccRCC. Univariate and multivariate Cox regression analysis showed that HSD11B2 expression was an independent prognostic factor. To establish a nomogram combining HSD11B2 expression and clinical factors, and a new method for predicting the survival probability of ccRCC patients. Gene Set Enrichment Analysis (GSEA) enrichment results showed that low expression of HSD11B2 was mainly enriched in tumor signaling pathways and immune-related pathways. Immune analysis revealed a significant correlation between HSD11B2 and tumor immune infiltrates in ccRCC. This study suggests that HSD11B2 can serve as a potential biomarker and therapeutic target for ccRCC metastasis.
Insights
This study identifies HSD11B2 as a key gene in clear cell renal cell carcinoma (ccRCC) metastasis. Down-regulation of HSD11B2 indicates poor prognosis and potential as a therapeutic target for ccRCC.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Metastasis of clear cell renal cell carcinoma (ccRCC) is a significant cause of cancer-related mortality.
- Identifying key genes driving ccRCC metastasis is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the key gene implicated in clear cell renal cell carcinoma (ccRCC) tumor metastasis.
- To evaluate the potential of HSD11B2 as a prognostic biomarker and therapeutic target in ccRCC.
Main Methods:
- Utilized microarray datasets (GSE22541, GSE85258, GSE105261) and The Cancer Genome Atlas (TCGA) data for differential gene expression analysis.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify enriched pathways.
- Employed GEPIA2, qRT-PCR, ROC analysis, and Cox regression for gene validation, diagnostic efficiency, and prognostic assessment.
Main Results:
- Identified 20 overlapping differentially expressed genes (DEGs) enriched in metastasis-related pathways.
- HSD11B2 was identified as a key gene, significantly down-regulated in ccRCC tissues and associated with poor prognosis.
- HSD11B2 demonstrated diagnostic efficiency and was an independent prognostic factor, correlating with tumor immune infiltrates.
Conclusions:
- HSD11B2 is a potential biomarker for predicting ccRCC metastasis and patient survival.
- Targeting HSD11B2 may offer a novel therapeutic strategy for clear cell renal cell carcinoma (ccRCC) metastasis.
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