Zhang Jinguo, Shan Benjie, Lin Lin, Dong Jie, Sun Qingqing, Zhou Qiong, Chen Jian, Han Xinghua
Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.
Front Cell Dev Biol. 2021 Oct 6;9:711859. doi: 10.3389/fcell.2021.711859. eCollection 2021.
Breast cancer (BC) represents a molecularly and clinically heterogeneous disease. Recent progress in immunotherapy has provided a glimmer of hope for several BC subtypes. The relationship between N6-methyladenosine (m6A) modification and long non-coding RNAs (LncRNAs) is still largely unexplored in BC. Here, with the intention to dissect the landscape of m6A-related lncRNAs and explore the immunotherapeutic value of the m6A-related lncRNA signature, we identified m6A-related lncRNAs by co-expression analysis from The Cancer Genome Atlas (TCGA) and stratified BC patients into different subgroups. Furthermore, we generated an m6A-related lncRNA prognostic signature. Four molecular subtypes were identified by consensus clustering. Cluster 3 preferentially had favorable prognosis, upregulated immune checkpoint expression, and high level of immune cell infiltration. Twenty-one m6A-related lncRNAs were applied to construct the m6A-related lncRNA model (m6A-LncRM). Survival analysis and receiver operating characteristic (ROC) curves further confirmed the prognostic value and prediction performance of m6A-LncRM. Finally, high- and low-risk BC subgroups displayed significantly different clinical features and immune cell infiltration status. Overall, our study systematically explored the prognostic value of the m6A-related LncRNAs and identified a high immunogenicity BC subtype. The proposed m6A-related LncRNA model might serve as a robust prognostic signature and attractive immunotherapeutic targets for BC treatment.
乳腺癌（BC）是一种分子和临床异质性疾病。免疫疗法的最新进展为几种BC亚型带来了一线希望。N6-甲基腺苷（m6A）修饰与长链非编码RNA（LncRNAs）之间的关系在BC中仍 largely未被探索。在此，为了剖析m6A相关lncRNAs的格局并探索m6A相关lncRNA特征的免疫治疗价值，我们通过来自癌症基因组图谱（TCGA）的共表达分析鉴定了m6A相关lncRNAs，并将BC患者分层为不同亚组。此外，我们生成了一个m6A相关lncRNA预后特征。通过一致性聚类鉴定出四种分子亚型。聚类3优先具有良好的预后、上调的免疫检查点表达和高水平的免疫细胞浸润。应用21种m6A相关lncRNAs构建m6A相关lncRNA模型（m6A-LncRM）。生存分析和受试者工作特征（ROC）曲线进一步证实了m6A-LncRM的预后价值和预测性能。最后，高风险和低风险BC亚组表现出明显不同的临床特征和免疫细胞浸润状态。总体而言，我们的研究系统地探索了m6A相关LncRNAs的预后价值，并鉴定出一种高免疫原性的BC亚型。所提出的m6A相关LncRNA模型可能作为一种强大的预后特征和有吸引力的免疫治疗靶点用于BC治疗。
