Multiomics integrative analysis for gene signatures and prognostic values of m(6)A regulators in pancreatic adenocarcinoma: a retrospective study in The Cancer Genome Atlas project.
Multiomics integrative analysis for gene signatures and prognostic values of m(6)A regulators in pancreatic adenocarcinoma: a retrospective study in The Cancer Genome Atlas project.
复制标题
胰腺癌中 m6A 调节因子的基因特征和预后价值的多组学综合分析：癌症基因组图谱项目的回顾性研究
DOI：
10.18632/aging.103942
复制
发表时间：
2020-10-20
期刊：
影响因子：
--
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Gao W;Cheng L;He S;Li W;Zhou C;Zhou B;Liu J;Xu J;Yu X;Zhu H
n6 -甲基腺苷（m6a）是真核生物中最丰富的转录后RNA修饰。然而，对其在胰腺腺癌（PAAD）中的作用知之甚少。我们研究的目的是确定PAAD中m6a调节因子的基因特征和预后价值。患者来自3个不同的数据集，具有完整的基因组和转录组测序数据。采用log-rank检验和Cox回归模型进行不同基因改变的生存分析。采用卡方检验检验m6a调节因子的改变与临床病理特征之间的关系。结果表明，PAAD患者中m6a调控基因拷贝数改变（CNAs）频率较高，但体细胞突变很少发生。CNAs和m6a调控基因突变与患者性别、病理分期和切除肿瘤大小有关。与其他模式相比，m6a“读取器”基因“功能获得”合并“写入器”或“擦除器”拷贝数缺失的患者的总生存期（OS）更差。此外，m6a“阅读器”基因胰岛素生长因子2结合蛋白2 （IGF2BP2）拷贝数增加是OS （HR= 2.392, 95% CI: 1.392-4.112, p< 0.001）和无病生存（DFS）（HR= 2.400, 95% CI: 1.236-4.659, p= 0.010）的独立危险因素。基因集富集分析（GSEA）表明，IGF2BP2与多种与癌症相关的生物学过程相关，其中最重要的过程与癌细胞周期、细胞永生化和肿瘤免疫相关。综上所述，m6a基因组改变与较差的临床结果之间存在显著关系。这些创新发现有望指导进一步研究m6a在PAAD中的作用机制。
N6-methyladenosine (m 6 A) is the most abundant post-transcriptional RNA modification in eukaryotes. However, little is known about its role in pancreatic adenocarcinoma (PAAD). The aim of our study was to identify gene signatures and prognostic values of m 6 A regulators in PAAD. Patients from 3 different datasets with complete genomic and transcriptomic sequencing data were enrolled. Survival analysis for different gene alterations was performed using log-rank tests and Cox regression model. The association between alteration of m 6 A regulators and clinicopathological characteristics was examined using chi-square test. Results showed a high frequency of copy number alterations (CNAs) of m 6 A regulatory genes in PAAD patients, but somatic mutations were rarely happened. CNAs and mutations of m 6 A regulatory genes was associated with patient’s gender, pathologic stage and resected tumor size. Patients with “gain of function” for m 6 A “reader” genes combined with copy number loss of “writers” or “erasers” had worse overall survival (OS) compared with other patterns. Moreover, copy number gain of m 6 A “reader” gene insulin growth factor 2 binding protein 2 (IGF2BP2) was an independent risk factor for OS (HR= 2.392, 95% CI: 1.392-4.112, p< 0.001) and disease-free survival (DFS)(HR= 2.400, 95% CI: 1.236-4.659, p= 0.010). Gene Set Enrichment Analysis (GSEA) indicated that IGF2BP2 was correlated with multiple biological processes associated with cancer, of which the most significant processes were relevant to cancer cell cycle, cell immortalization and tumor immunity. To sum up, a significant relationship was found between m 6 A genomic alterations and worse clinical outcomes. These innovative findings are expected to guide further research on the mechanism of m 6 A in PAAD.
登录
查看更多内容
YTHDF2 通过直接招募 CCR4-NOT 去腺苷酶复合物来破坏含有 m(6)A 的 RNA 的稳定性。
影响因子：
16.6
作者：
Du, Hao;Zhao, Ya;He, Jinqiu;Zhang, Yao;Xi, Hairui;Liu, Mofang;Ma, Jinbiao;Wu, Ligang
通讯作者：
Wu, Ligang
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
64.5
作者：
Meyer KD;Saletore Y;Zumbo P;Elemento O;Mason CE;Jaffrey SR
通讯作者：
Jaffrey SR
影响因子：
14.9
作者：
DUBIN, DT;TAYLOR, RH
通讯作者：
TAYLOR, RH
影响因子：
64.8
作者：
Bailey, Peter;Chang, David K.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.