Lv Wenchang, Wang Yichen, Zhao Chongru, Tan Yufang, Xiong Mingchen, Yi Yi, He Xiao, Ren Yuping, Wu Yiping, Zhang Qi
Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2021 Oct 15;11:745719. doi: 10.3389/fonc.2021.745719. eCollection 2021.
The metastasis and poor prognosis are still regarded as the main challenge in the clinical treatment of breast cancer (BC). Both N6-methyladenosine (m6A) modification and lncRNAs play vital roles in the carcinogenesis and evolvement of BC. Considering the unknown association of m6A and lncRNAs in BC, this study therefore aims to discern m6A-related lncRNAs and explore their prognostic value in BC patients. Firstly, a total of 6 m6A-related lncRNAs were screened from TCGA database and accordingly constructed a prognostic-predicting model. The BC patients were then divided into high-risk and low-risk groups dependent on the median cutoff of risk score based on this model. Then, the predictive value of this model was validated by the analyses of cox regression, Kaplan-Meier curve, ROC curve, and the biological differences in the two groups were validated by PCA, KEGG, GSEA, immune status as well as assay. Finally, we accordingly constructed a risk prognostic model based on the 6 identified m6A-related lncRNAs, including Z68871.1, AL122010.1, OTUD6B-AS1, AC090948.3, AL138724.1, EGOT. Interestingly, the BC patients were divided into the low-risk and high-risk groups with different prognoses according to the risk score. Notably, the risk score of the model was an excellent independent prognostic factor. In the clinical sample validation, m6A regulatory proteins were differentially expressed in patients with different risks, and the markers of tumor-associated macrophages and m6A regulators were co-localized in high-risk BC tissues. This well-validated risk assessment tool based on the repertoire of these m6A-related genes and m6A-related lncRNAs, is of highly prognosis-predicting ability, and might provide a supplemental screening method for precisely judging BC prognosis.
转移和预后不良仍然是乳腺癌（BC）临床治疗中的主要挑战。N6-甲基腺苷（m6A）修饰和长链非编码RNA（lncRNAs）在BC的发生发展中都起着至关重要的作用。鉴于m6A与lncRNAs在BC中的关联尚不清楚，本研究旨在识别与m6A相关的lncRNAs，并探索它们在BC患者中的预后价值。首先，从TCGA数据库中筛选出总共6个与m6A相关的lncRNAs，并据此构建了一个预后预测模型。然后，根据该模型的风险评分中位数临界值，将BC患者分为高风险组和低风险组。接着，通过cox回归分析、Kaplan-Meier曲线、ROC曲线验证了该模型的预测价值，并通过主成分分析（PCA）、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）、免疫状态以及检测验证了两组之间的生物学差异。最后，我们据此构建了一个基于6个已鉴定的与m6A相关的lncRNAs（包括Z68871.1、AL122010.1、OTUD6B-AS1、AC090948.3、AL138724.1、EGOT）的风险预后模型。有趣的是，根据风险评分，BC患者被分为预后不同的低风险组和高风险组。值得注意的是，该模型的风险评分是一个出色的独立预后因素。在临床样本验证中，m6A调节蛋白在不同风险的患者中差异表达，并且肿瘤相关巨噬细胞和m6A调节因子的标志物在高风险BC组织中共定位。这种基于这些与m6A相关的基因和与m6A相关的lncRNAs的有效风险评估工具具有高度的预后预测能力，可能为准确判断BC预后提供一种补充筛查方法。
