Gu Yun, Xu Min, Wu Wangfei, Ma Zhifang, Liu Weiguang
Department of Pathology, Nanjing Women and Children's Healthcare Hospital, Women's Hospital of Nanjing Medical University, Tianfei Road 123th, Nanjing, 210004, Jiangsu, China.
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Biochem Genet. 2024 Jul 23. doi: 10.1007/s10528-024-10889-0.
Breast cancer represents the predominant malignant neoplasm in women, posing significant threats to both life and health. N6-methyladenosine (m6A) methylation, the most prevalent RNA modification, plays a crucial role in cancer development. This study aims to delineate the prognostic implications of m6A-associated long non-coding RNAs (m6AlncRNAs) and identify potential m6AlncRNA candidates as novel therapeutic targets for breast cancer. Through univariate Cox, Least Absolute Shrinkage and Selection Operator and multiple Cox regression analysis, m6AlncRNA was analyzed and a risk-prognosis model was constructed. Kaplan-Meier analysis, principal component analysis and nomogram were used to evaluate the risk model. Finally, we screened candidate lncRNAs and validated them in breast cancer cell lines. m6AlncRNAs were stratified into three subtypes, and their associations with survival outcomes and immune infiltrating capacities were systematically analyzed. Subsequently, breast cancer patients were stratified into high and low-risk groups based on median risk scores, revealing distinct clinical characteristics, tumor immunoinvasive profiles, tumor mutation burden, and survival probabilities. Additionally, a prognostic model was established, highlighting three promising candidate lncRNAs: ECE1-AS1, NDUFA6-DT, and COL4A2-AS1. This study investigated the prognostic implications of m6A-associated long non-coding RNAs (m6AlncRNAs) and developed a prognostic risk model to identify three potential m6AlncRNA candidates. These findings provide valuable insights into the potential application of these m6AlncRNAs in guiding immunotherapeutic strategies for breast cancer.
乳腺癌是女性中最主要的恶性肿瘤，对生命和健康构成重大威胁。N6-甲基腺苷（m6A）甲基化是最普遍的RNA修饰，在癌症发展中起关键作用。本研究旨在阐明m6A相关长链非编码RNA（m6AlncRNAs）的预后意义，并鉴定潜在的m6AlncRNA候选物作为乳腺癌的新型治疗靶点。通过单因素Cox分析、最小绝对收缩和选择算子以及多因素Cox回归分析，对m6AlncRNA进行分析并构建风险预后模型。采用Kaplan-Meier分析、主成分分析和列线图评估风险模型。最后，我们筛选了候选lncRNAs并在乳腺癌细胞系中进行验证。m6AlncRNAs被分为三个亚型，并系统分析了它们与生存结果和免疫浸润能力的关联。随后，根据中位风险评分将乳腺癌患者分为高风险组和低风险组，揭示了不同的临床特征、肿瘤免疫侵袭特征、肿瘤突变负荷和生存概率。此外，建立了一个预后模型，突出了三个有前景的候选lncRNAs：ECE1-AS1、NDUFA6-DT和COL4A2-AS1。本研究调查了m6A相关长链非编码RNA（m6AlncRNAs）的预后意义，并开发了一种预后风险模型来鉴定三个潜在的m6AlncRNA候选物。这些发现为这些m6AlncRNAs在指导乳腺癌免疫治疗策略中的潜在应用提供了有价值的见解。
