Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong, China.
Department of Internal Medicine, The Third People's Hospital of Linyi, Linyi, Shandong, China.
J Cell Physiol. 2020 Oct;235(10):6574-6581. doi: 10.1002/jcp.29517. Epub 2020 Feb 5.
Breast carcinoma is one of the most commonly diagnosed tumors and also one of the deadliest cancers in the female. Long noncoding RNAs (lncRNAs) are emerging as novel targets and biomarkers for breast cancer diagnosis and treatment. In this study, we aimed to study the lncRNAs associated with the outcomes in patients using the breast invasive carcinoma datasets from The Cancer Genome Atlas. The Cox proportional hazards regression model was fitted to each lncRNA. Hierarchy clustering was carried out using these survival-related lncRNAs and the log-rank test was carried out for the clustered groups. DNA methylation status was utilized to identify the lncRNAs regulated by epigenetics. Finally, the coexpressed messenger RNA with the potential lncRNAs were utilized to study the possible functions and mechanisms of lncRNAs. In total, 182 lncRNAs had an impact on the survival time of the patients with a cutoff <0.01. The patients were clustered into three groups using these survival-related genes, which performed significantly different prognosis. Two lncRNAs, which were significantly correlated with the outcomes of breast cancer and were regulated by methylation status, were obtained. These two lncRNAs were TP53TG1 and RP5-1061H20.4. We proposed that TP53TG1 was activated by the wild-type TP53 and performed an impact on the PI3Ks family by binding YBX2 in breast cancer.
乳腺癌是女性最常见的诊断肿瘤之一，也是最致命的癌症之一。长链非编码 RNA（lncRNA）正在成为乳腺癌诊断和治疗的新靶点和生物标志物。在这项研究中，我们旨在使用来自癌症基因组图谱的乳腺浸润性癌数据集研究与患者结局相关的 lncRNA。对每个 lncRNA 进行 Cox 比例风险回归模型拟合。使用这些与生存相关的 lncRNA 进行层次聚类，并对聚类组进行对数秩检验。利用 DNA 甲基化状态鉴定受表观遗传学调控的 lncRNA。最后，利用与潜在 lncRNA 共表达的信使 RNA 来研究 lncRNA 的可能功能和机制。共有 182 个 lncRNA 对患者的生存时间有影响，截止值<0.01。使用这些与生存相关的基因将患者聚类为三组，这三组患者的预后差异显著。获得了两个与乳腺癌结局显著相关且受甲基化状态调控的 lncRNA，即 TP53TG1 和 RP5-1061H20.4。我们提出 TP53TG1 由野生型 TP53 激活，并通过与 YBX2 结合在乳腺癌中对 PI3Ks 家族产生影响。
