Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma

Abstract Background Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features...

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Main Authors: Bin Zhao, Yanqiu You, Zheng Wan, Yunhan Ma, Yani Huo, Hongyi Liu, Yuanyuan Zhou, Wei Quan, Weibin Chen, Xiaohong Zhang, Fujun Li, Yilin Zhao
Format: Article
Language:English
Published: BMC 2019-03-01
Series:BMC Medical Genetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12881-019-0791-1
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author Bin Zhao
Yanqiu You
Zheng Wan
Yunhan Ma
Yani Huo
Hongyi Liu
Yuanyuan Zhou
Wei Quan
Weibin Chen
Xiaohong Zhang
Fujun Li
Yilin Zhao
author_facet Bin Zhao
Yanqiu You
Zheng Wan
Yunhan Ma
Yani Huo
Hongyi Liu
Yuanyuan Zhou
Wei Quan
Weibin Chen
Xiaohong Zhang
Fujun Li
Yilin Zhao
author_sort Bin Zhao
collection DOAJ
description Abstract Background Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF. Methods Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database. Results We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process. Conclusion In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.
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spelling doaj.art-35b972f5b4a944ce8c3951abb5f277722022-12-21T18:34:51ZengBMCBMC Medical Genetics1471-23502019-03-0120111010.1186/s12881-019-0791-1Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanomaBin Zhao0Yanqiu You1Zheng Wan2Yunhan Ma3Yani Huo4Hongyi Liu5Yuanyuan Zhou6Wei Quan7Weibin Chen8Xiaohong Zhang9Fujun Li10Yilin Zhao11School of Medicine, Xiamen UniversityThe Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversitySchool of Medicine, Xiamen UniversityThe Department of Anesthesiology, the First Affiliated Hospital of Harbin Medical UniversitySchool of Medicine, Xiamen UniversityAbstract Background Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF. Methods Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database. Results We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF. For further validation, three of these genes (CYR61, DUSP1, and RNASE4) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process. Conclusion In this study, CYR61, DUSP1, and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma.http://link.springer.com/article/10.1186/s12881-019-0791-1Weighted gene co-expression network analysisDifferentially expressed genesOverall survivalMelanomaBRAF gene
spellingShingle Bin Zhao
Yanqiu You
Zheng Wan
Yunhan Ma
Yani Huo
Hongyi Liu
Yuanyuan Zhou
Wei Quan
Weibin Chen
Xiaohong Zhang
Fujun Li
Yilin Zhao
Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
BMC Medical Genetics
Weighted gene co-expression network analysis
Differentially expressed genes
Overall survival
Melanoma
BRAF gene
title Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
title_full Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
title_fullStr Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
title_full_unstemmed Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
title_short Weighted correlation network and differential expression analyses identify candidate genes associated with BRAF gene in melanoma
title_sort weighted correlation network and differential expression analyses identify candidate genes associated with braf gene in melanoma
topic Weighted gene co-expression network analysis
Differentially expressed genes
Overall survival
Melanoma
BRAF gene
url http://link.springer.com/article/10.1186/s12881-019-0791-1
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