Increased expression of YTHDF1 and HNRNPA2B1 as potent biomarkers for melanoma: a systematic analysis
Increased expression of YTHDF1 and HNRNPA2B1 as potent biomarkers for melanoma: a systematic analysis
复制标题
YTHDF1 和 HNRNPA2B1 表达增加作为黑色素瘤的有效生物标志物：系统分析
DOI：
10.1186/s12935-020-01309-5
复制
发表时间：
2020-06-15
影响因子：
5.8
通讯作者：
Qian, Cheng
中科院分区：
文献类型：
--
作者：
Li, Tengda;Gu, Mingli;Qian, Cheng
背景黑色素瘤的发病率和死亡率在全球范围内呈上升趋势。为了深入解释其机制，我们进行了系统的分析，检测了常见的RNA表观遗传修饰-N6-甲基腺苷(M6A)在黑色素瘤患者中的调控基因水平，并与健康人进行了比较。方法基于Oncomine上公开的数据集，我们分析了m6A Eraser、Writer和Reader基因的表达，并用基因表达综合数据集对结果进行了验证。结果发现YTHDF1和hnRNPA2B1在黑色素瘤中表达上调。与单独使用两种基因相比，结合这两种基因可将诊断黑色素瘤的效率提高约10%。对4种分析方法鉴定的HUB基因进行比较，筛选出重叠基因。这些基因在几个基因本体论术语中都得到了丰富。与P53信号相关的基因包括CDK2、CDK1、RRM2、CCNB1和CHEK1。所有五个基因都与YTHDF1或hnRNPA2B1呈正相关，表明这两个基因都可能影响这五个基因对m6A的修饰，进一步上调它们的表达，促进它们在抑制P53抑制肿瘤发生中的作用。我们还观察到YTHDF1和hnRNPA2B1的主要突变导致它们在黑色素瘤中放大。M6A基因突变患者与未突变患者在肿瘤分期、治疗反应等临床特征上存在显著差异。结论首次发现m6A调控基因组合可用于黑色素瘤的诊断。我们还在系统完整的数据基础上，对m6A相关基因进行了较为全面的分析。我们发现YTHDF1和hnRNPA2B1在黑色素瘤中发生了改变，并可能通过P53等信号通路影响疾病的发展。
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.