Abstract
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.
Highlights
As one of the deadliest forms of cancer, cutaneous melanoma is responsible for more than 75% of deaths among all cutaneous cancers and no less than 5% of cases of cutaneous cancer (Rebecca et al, 2020)
Cutaneous melanoma refers to the malignant transformation of melanocytes, a type of cell that produces melanin and regulates the absorption of ultraviolet radiation (UVR) and skin pigmentation (Lin and Fisher, 2007)
It is noteworthy that the m6A RNA methylation regulators are necessary in the occurrence and development of cancer
Summary
As one of the deadliest forms of cancer, cutaneous melanoma is responsible for more than 75% of deaths among all cutaneous cancers and no less than 5% of cases of cutaneous cancer (Rebecca et al, 2020). Cutaneous melanoma refers to the malignant transformation of melanocytes, a type of cell that produces melanin and regulates the absorption of ultraviolet radiation (UVR) and skin pigmentation (Lin and Fisher, 2007). Known for its high levels of aggressiveness and therapy resistance, cutaneous melanoma was considered to be untreatable before several checkpoint inhibitor therapies were approved, which later proved to show remarkable improvements. Approximately 70% of cutaneous melanoma patients and their attending physicians still face the challenges of immune checkpoint inhibitor (ICI) resistance, high mortality rates, recurrence, and dissemination (Jerby-Arnon et al, 2018). 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 evaluated gene mutations in cutaneous melanoma
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