Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer
Identification and validation of m6A RNA methylation regulators with clinical prognostic value in Papillary thyroid cancer
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m(6)A RNA 甲基化调节因子的鉴定和验证对甲状腺乳头状癌具有临床预后价值。
DOI：
10.1186/s12935-020-01283-y
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发表时间：
2020-05-29
影响因子：
5.8
通讯作者：
Lv, Yunxia
中科院分区：
文献类型：
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作者：
Wang, Xinyi;Fu, Xiaorui;Lv, Yunxia
背景：甲状腺乳头状癌（PTC）是一种预后良好的恶性肿瘤，占甲状腺癌的80%以上。方法：从美国癌症基因组图谱（TCGA）下载数据，分析19个m（6）A RNA甲基化调控因子在PTC中的RNA表达、单核苷酸多态性（SNP）和拷贝数变异（CNVs）。然后，我们使用非负矩阵因子分解（NMF）将患者聚类为两种m（6）A亚型，并比较它们的总生存期（OS）和无病生存期（DFS）。采用加权相关网络分析（WGCNA）和单变量考克斯比例风险模型（CoxPH）筛选用于构建m（6）A相关标签的基因。通过受试者工作特征（ROC）曲线、K-M（Kaplan-Meier）生存分析、单变量和多变量分析，验证了该标记的准确性和预后价值。尤其是IGF 2BP 2（胰岛素样生长因子2 mRNA结合蛋白2），其在肿瘤组织中最显著地过表达。我们从WGCNA中选择了m（6）A相关模块中的4个基因：IGF 2BP 2、STT 3A、MTHFD 1和GSTM 4，并使用它们构建了m（6）A相关标签。该特征的预后价值得到了验证，特征提供的风险评分是PTC的独立预后因素。结论：我们对PTC的m（6）A RNA修饰景观进行了全面的评估，并探讨了其潜在的机制。我们的m（6）A相关特征对预测PTC患者的DFS具有重要意义。IGF 2BP 2基因与PTC的DFS和临床表型密切相关，值得进一步研究。
Background: Papillary thyroid cancer (PTC) is a type of malignant tumor with excellent prognosis, accounting for more than 80% of thyroid cancer. Recently, numerous studies illustrated the importance of N-6-methyladenosine (m(6)A) RNA modification to tumorigenesis, but it has never been reported in PTC.Methods: We downloaded data from The Cancer Genome Atlas (TCGA) and analyzed RNA expression, single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) of 19 m(6)A RNA methylation regulators in PTC. Then we used nonnegative matrix factorization (NMF) to cluster patients into two m(6)A subtypes and compared them in overall survival (OS) and disease-free survival (DFS). The Weighted correlation network analysis (WGCNA) and univariate Cox proportional hazard model (CoxPH) were used to select genes for the construction of a m(6)A-related signature. The accuracy and prognostic value of this signature were validated by using receiver operating characteristic (ROC) curves, K-M (Kaplan-Meier) survival analysis, univariant and multivariant analyses.Results: CNVs and differential expression of m(6)A regulators were observed in PTC patients. Especially IGF2BP2 (Insulin-like growth factor 2 mRNA binding protein 2), which was most significantly overexpressed in tumor tissue. We chose 4 genes in the m(6)A-related module from WGCNA: IGF2BP2, STT3A, MTHFD1 and GSTM4, and used them to construct a m(6)A-related signature. The prognostic value of this signature was validated, and risk scores provided by the signature was the independent prognostic factor for PTC. A nomogram was also provided for clinical usage.Conclusions: We performed a comprehensive evaluation of the m(6)A RNA modification landscape of PTC and explored its underlying mechanisms. Our m(6)A-related signature was of great significance in predicting the DFS of patients with PTC. And IGF2BP2 was a gene worthy for further analysis as its strong correlation with DFS and clinical phenotypes of PTC.