Expression and Prognostic Characteristics of m(6) A RNA Methylation Regulators in Breast Cancer.
Expression and Prognostic Characteristics of m(6) A RNA Methylation Regulators in Breast Cancer.
复制标题
m(6) A RNA 甲基化调节因子在乳腺癌中的表达和预后特征
DOI：
10.3389/fgene.2020.604597
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发表时间：
2020
影响因子：
3.7
通讯作者：
Jiang G
中科院分区：
文献类型：
--
作者：
Zhang B;Gu Y;Jiang G
N6-甲基腺苷（m6A）是mRNA甲基化中最常见的修饰，其对生物学功能具有广泛的影响。本研究旨在确定基于m6A RNA甲基化调节因子的生物标志物在乳腺癌中的预后意义。首先通过ONCOMINE分析23个RNA甲基化调节子，然后从癌症基因图谱（TCGA）数据库中获取1,096例乳腺癌和112例正常组织的相关RNA-seq转录组和临床数据。基因表达综合数据库（GEO）也显示了表达差异。从基因型-组织表达（GTEx）数据库获得人组织中m6A RNA调节剂的基因表达数据。应用R v3.5.1和其他在线工具如STRING、bc-GeneExminer v4.5、Kaplan-Meier Plotter进行生物信息学分析。ONCOMINE、TCGA和GEO数据库的结果显示，乳腺癌患者中m6 A RNA甲基化调节因子的独特表达和临床相关性。YTHDF3、ZC3H13、LRPPRC和胃L16的高表达表明乳腺癌患者的生存率低，而RBM15 B的高表达表明生存率较好。单变量和多变量考克斯回归分析均显示年龄和风险评分与总生存期（OS）相关。Kaplan-Meier Plotter平台从另一个角度分析显示，乳腺癌患者中YTHDF 3和LRPPRC的相对高表达和RBM15 B、ZC 3H13和胃L16的相对低表达具有较差的无复发生存期（RFS）。乳腺癌基因表达Miner v4.5显示LRPPRC水平与ER、PR表达呈负相关，而L16、RBM15 B、ZC3H13水平与ER、PR表达呈正相关。在HER-2（+）乳腺癌患者中，LRPPRC、胃L16、RBM15 B和ZC3H13的表达均低于HER-2（-）组。本研究分析并验证了m6A RNA甲基化调节因子表达水平的显著差异和预后价值。该特征揭示了m6A RNA甲基化调节剂在乳腺癌中的潜在治疗价值。
N6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer. The 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis. Results from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group. The significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.