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鉴定与N6-甲基腺苷相关的长链非编码RNA以预测乳腺癌的总生存期及一种潜在新型分子亚型的聚类分析

Identification of N6-Methyladenosine-Related LncRNAs for Predicting Overall Survival and Clustering of a Potentially Novel Molecular Subtype of Breast Cancer.

作者信息

Zhong Xiaoxiao, Li Jun, Wu Xin, Wu Xianrui, Hu Lin, Ding Boni, Qian Liyuan

机构信息

Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, China.

Department of Spine Surgery, Third Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Oncol. 2021 Oct 15;11:742944. doi: 10.3389/fonc.2021.742944. eCollection 2021.

Abstract

We aimed to identify a signature comprising N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and molecular subtypes associated with breast cancer (BRCA). We obtained data of BRCA samples from The Cancer Genome Atlas database. The m6A-related lncRNA prognostic signature (m6A-LPS) included 10 lncRNAs previously identified as prognostic m6A-related lncRNAs and was constructed using integrated bioinformatics analysis and validated. Accordingly, a risk score based on the m6A-LPS signature was established and shown to confirm differences in survival between high-risk and low-risk groups. Three distinct genotypes were identified, whose characteristics included features of the tumor immune microenvironment in each subtype. Our results indicated that patients in Cluster 2 might have a worse prognostic outcome than those in other clusters. The three genotypes and risk subgroups were enriched in different biological processes and pathways, respectively. We then constructed a competing endogenous RNA network based on the prognostic m6A-related lncRNAs. Finally, we validated the expression levels of target lncRNAs in 72 clinical samples. In summary, the m6A-LPS and the potentially novel genotype may provide a theoretical basis for further study of the molecular mechanism of BRCA and may provide novel insights into precision medicine.

摘要

我们旨在鉴定一个包含N6-甲基腺苷(m6A)相关长链非编码RNA(lncRNA)的特征以及与乳腺癌(BRCA)相关的分子亚型。我们从癌症基因组图谱数据库获取了BRCA样本的数据。m6A相关lncRNA预后特征(m6A-LPS)包括10个先前被鉴定为预后m6A相关lncRNA的lncRNA,并通过综合生物信息学分析构建并验证。据此,建立了基于m6A-LPS特征的风险评分,并显示其证实了高风险组和低风险组之间的生存差异。鉴定出三种不同的基因型,其特征包括每个亚型中肿瘤免疫微环境的特征。我们的结果表明,聚类2中的患者预后可能比其他聚类中的患者更差。这三种基因型和风险亚组分别富集于不同的生物学过程和途径。然后,我们基于预后m6A相关lncRNA构建了一个竞争性内源性RNA网络。最后,我们验证了72个临床样本中靶lncRNA的表达水平。总之,m6A-LPS和潜在的新基因型可能为进一步研究BRCA的分子机制提供理论基础,并可能为精准医学提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd0b/8554333/0def6df12696/fonc-11-742944-g001.jpg

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