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

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 Information
  1. Bin Zhao: School of Medicine, Xiamen University, Xiamen, Fujian, China. ORCID
  2. Yanqiu You: The Department of Clinical Laboratory, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  3. Zheng Wan: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  4. Yunhan Ma: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  5. Yani Huo: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  6. Hongyi Liu: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  7. Yuanyuan Zhou: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  8. Wei Quan: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  9. Weibin Chen: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  10. Xiaohong Zhang: School of Medicine, Xiamen University, Xiamen, Fujian, China.
  11. Fujun Li: The Department of Anesthesiology, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
  12. Yilin Zhao: School of Medicine, Xiamen University, Xiamen, Fujian, China. zyllbz@gmail.com.

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.

Keywords

References

  1. Mol Med Rep. 2017 Dec;16(6):8441-8447 [PMID: 28983624]
  2. Nature. 1992 Oct 15;359(6396):644-7 [PMID: 1406996]
  3. Nucleic Acids Res. 1995 Nov 11;23(21):4290-5 [PMID: 7501448]
  4. Cancer Immunol Immunother. 2012 May;61(5):733-7 [PMID: 22382362]
  5. Stat Appl Genet Mol Biol. 2005;4:Article17 [PMID: 16646834]
  6. BMC Bioinformatics. 2008 Dec 29;9:559 [PMID: 19114008]
  7. Oncol Rep. 2018 Sep;40(3):1203-1222 [PMID: 29956792]
  8. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4015-20 [PMID: 23431193]
  9. Bioinformatics. 2019 Jan 1;35(1):62-68 [PMID: 30561551]
  10. Nature. 2014 Sep 4;513(7516):105-9 [PMID: 25079330]
  11. Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102 [PMID: 28407145]
  12. Cell Mol Life Sci. 2011 Oct;68(19):3149-63 [PMID: 21805345]
  13. Bioinformatics. 2014 Sep 1;30(17):2534-6 [PMID: 24764463]
  14. Mol Med Rep. 2017 Nov;16(5):6499-6505 [PMID: 28901407]
  15. Ann Appl Stat. 2016 Jun;10(2):946-963 [PMID: 28367255]
  16. Nucleic Acids Res. 2003 May 1;31(9):e52 [PMID: 12711697]
  17. Cancer Res. 2008 Feb 1;68(3):664-73 [PMID: 18245465]
  18. Nature. 2014 Nov 20;515(7527):S109 [PMID: 25407704]
  19. Oncogene. 2011 Feb 10;30(6):668-78 [PMID: 20890299]
  20. Clin Cancer Res. 2010 Dec 1;16(23):5908-13 [PMID: 21138874]
  21. Biomed Res Int. 2018 Sep 26;2018:4246703 [PMID: 30356407]
  22. Surg Clin North Am. 2014 Oct;94(5):945-62, vii [PMID: 25245960]
  23. Nat Rev Drug Discov. 2011 Dec 01;10(12):945-63 [PMID: 22129992]
  24. Cancer Res. 2014 Dec 15;74(24):7191-7 [PMID: 25312268]

MeSH Term

Cysteine-Rich Protein 61
Dual Specificity Phosphatase 1
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genetic Association Studies
Humans
Melanoma
Mutation
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins B-raf
Ribonucleases
Skin Neoplasms
Survival Analysis
Melanoma, Cutaneous Malignant

Chemicals

CCN1 protein, human
Cysteine-Rich Protein 61
BRAF protein, human
Proto-Oncogene Proteins B-raf
Ribonucleases
ribonuclease 4
DUSP1 protein, human
Dual Specificity Phosphatase 1

Word Cloud

Created with Highcharts 10.0.0genesmelanomaexpressionBRAFgenenetworkanalysisskinmutationsurvivalTCGAthreecutaneousMelanomaidentifypotentialinvolvedstatusdatasetsweightedco-expressionexpressedDEGsoverallGTExcorrelationdifferentialanalysesdatasamplesidentifiedCYR61DUSP1RNASE4foundassociatedfuturemolecularcandidateWeightedBACKGROUND:PrimarymalignantcancerpigmentcellsaccompaniedincidencemortalityratesrisingaroundworldcurrentknowledgepathogenesisclinicalgeneticfeaturesclearaimusebioinformaticskeyMETHODS:FirstlyusedUCSCpublichubLinetalCancerRes683:6642008performWGCNAdifferentiallyrespectivelySecondlyoverlappingsignificantmodulesscreenedvalidatedtranscriptionallevelsLastlyfunctionalenrichmentaccomplishedfindbiologicalfunctionsweb-serverdatabaseRESULTS:performedusing20whosecorrelatedvalidationsimilarpatternstumorscomparednormalalsoweakworsenucleicacidmetabolicprocessCONCLUSION:studyintereststudiesimproveunderstandingcausesunderlyingeventsmayprovidepromisingavenueresearchtherapeutictargetsDifferentiallyOverall

Similar Articles

Cited By (8)