Increased expression of YTHDF1 and HNRNPA2B1 as potent biomarkers for melanoma: a systematic analysis

Tengda Li,Anmei Deng,Mingli Gu,Cheng Qian

doi:10.1186/s12935-020-01309-5

Abstract

BackgroundThe incidence and mortality of melanoma is increasing around the world. To deeply explain the mechanism insight into it, we conducted a systematic analysis to examine the levels of regulatory genes of the common RNA epigenetic modification-N6-methyladenosine (m6A) in patients with melanoma compared by the healthy.MethodsWe analyzed the expression of m6A Eraser, Writer, and Reader genes based on publicly available datasets on Oncomine and validated the results with a gene expression omnibus dataset. Hub genes were identified with Cytohubba and the frequency of copy number alterations was analyzed with the cBioPortal tool.ResultsThe results revealed the up-regulation of YTHDF1 and HNRNPA2B1 in melanoma. Combining the two genes improved the efficacy in diagnosing melanoma by about 10% compared to each gene alone. Hub genes identified with four analysis methods were compared and the overlapping genes were selected. These genes were enriched in several gene ontology terms. Genes related to p53-signaling consisted of CDK2, CDK1, RRM2, CCNB1, and CHEK1. All five genes were positively correlated with either YTHDF1 or HNRNPA2B1, suggesting that both genes may affect m6A modification by the five genes, further up-regulating their expression and facilitate their roles in inhibiting p53 to suppress tumorigenesis. We also observed major mutations in YTHDF1 and HNRNPA2B1 that led to their amplification in melanoma. Significant differences were observed in the clinical characteristics of patients with altered and unaltered m6A regulatory genes such as tumor stage and treatment response.ConclusionsWe, for the first time, identified a combination of m6A regulatory genes to diagnose melanoma. We also analyzed m6A-related genes more comprehensively based on systematic complete data. We found that YTHDF1 and HNRNPA2B1 were altered in melanoma and might influence the development of the disease through signaling pathways such as p53.

Highlights

The incidence and mortality of melanoma is increasing around the world
Systematic comparison of m6A regulatory genes in melanoma and normal populations We used the Oncomine database to compare the expression of m6A-related genes in patients with melanoma and healthy individuals reported in five studies
We excluded the datasets if : they were without clinical information; the samples’ type was cell line or primary cell culture; their gene expression files were not provided on the Oncomine portal; they did not have samples of both patients with melanoma and the healthy

Summary

Introduction

The incidence and mortality of melanoma is increasing around the world. To deeply explain the mechanism insight into it, we conducted a systematic analysis to examine the levels of regulatory genes of the common RNA epigenetic modification-N6-methyladenosine (m6A) in patients with melanoma compared by the healthy. Melanoma is one of the fastest developing malignancies with strong aggressive ability, no proper curative treatments exist at present [1, 2]. It is a type of epithelial malignant tumor originating from melanocytes with obviously increasing incidence and mortality around the world [1]. With the advancement of sequencing technology, related mutations such as B-Raf proto-oncogene (BRAF) and signaling pathways such as the mitogen-activated protein kinase (MAPK) pathway have been found These discoveries have led to the emergence of targeted drug treatment for melanoma such as inhibitors of BRAF, mitogen-activated protein kinase kinase 7 (MAP2K7, known as MEK), and mitogen-activated protein kinase 1 (MAPK1, known as ERK) [2, 4, 5].

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