Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma

Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.Methods: We downloade...

Full description

Bibliographic Details
Main Authors: Zi-Yi Feng, Ting Wang, Xin Su, Shu Guo
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.665222/full
_version_ 1818439245284507648
author Zi-Yi Feng
Ting Wang
Xin Su
Shu Guo
author_facet Zi-Yi Feng
Ting Wang
Xin Su
Shu Guo
author_sort Zi-Yi Feng
collection DOAJ
description Background: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out.Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor.Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.
first_indexed 2024-12-14T17:53:24Z
format Article
id doaj.art-a33de9901a8147999e48b2529304b9f0
institution Directory Open Access Journal
issn 2296-889X
language English
last_indexed 2024-12-14T17:53:24Z
publishDate 2021-07-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Molecular Biosciences
spelling doaj.art-a33de9901a8147999e48b2529304b9f02022-12-21T22:52:35ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-07-01810.3389/fmolb.2021.665222665222Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous MelanomaZi-Yi FengTing WangXin SuShu GuoBackground: The purpose of our research was to establish a gene signature and determine the prognostic value of m6A methylation regulators in cutaneous melanoma and WTAP as a protective gene in cutaneous melanoma prognosis, we also evaluated gene mutations in cutaneous melanoma.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for cutaneous melanoma patients from the GTEx and TCGA databases. Consensus clustering analysis was applied to divide the samples into two groups. Then the least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature, and we use external and internal datasets to verify its predictive value. We further searched the cBioPortal tools to detect genomic alterations and WTAP mutations. Finally, WTAP was further identified as a prognostic factor, and the related mechanisms mediated by WTAP were predicted by gene set enrichment analysis (GSEA). Experimental validations and have been further carried out.Results: Notably, m6A RNA methylation regulators play significant roles in tumorigenesis and development. In total, we selected three subtypes of cutaneous melanoma according to consensus clustering of the m6A RNA methylation regulators, and the stage of cutaneous melanoma was proven to be related to the subtypes. The Cox regression and LASSO analyses built a risk signature including ELF3, ZC3H13 and WTAP. The prognostic value of the risk signature in internal and external datasets have been proven then. The whole-genome and selected gene WTAP mutations were further explored. WTAP as a single prognostic factor was also explored and found to serve as an independent protective prognostic factor.Conclusions: Our study constructed a stable risk signature composed of m6A RNA methylation regulators in cutaneous melanoma. Moreover, WTAP was identified as a valuable prognostic factor and potential molecular target for cutaneous melanoma treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2021.665222/fullcutaneous melanomam6A regulatorsWTAPbiomarkersurvival analysisgenomic alterations
spellingShingle Zi-Yi Feng
Ting Wang
Xin Su
Shu Guo
Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
Frontiers in Molecular Biosciences
cutaneous melanoma
m6A regulators
WTAP
biomarker
survival analysis
genomic alterations
title Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
title_full Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
title_fullStr Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
title_full_unstemmed Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
title_short Identification of the m6A RNA Methylation Regulators WTAP as a Novel Prognostic Biomarker and Genomic Alterations in Cutaneous Melanoma
title_sort identification of the m6a rna methylation regulators wtap as a novel prognostic biomarker and genomic alterations in cutaneous melanoma
topic cutaneous melanoma
m6A regulators
WTAP
biomarker
survival analysis
genomic alterations
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.665222/full
work_keys_str_mv AT ziyifeng identificationofthem6arnamethylationregulatorswtapasanovelprognosticbiomarkerandgenomicalterationsincutaneousmelanoma
AT tingwang identificationofthem6arnamethylationregulatorswtapasanovelprognosticbiomarkerandgenomicalterationsincutaneousmelanoma
AT xinsu identificationofthem6arnamethylationregulatorswtapasanovelprognosticbiomarkerandgenomicalterationsincutaneousmelanoma
AT shuguo identificationofthem6arnamethylationregulatorswtapasanovelprognosticbiomarkerandgenomicalterationsincutaneousmelanoma