Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients.
Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients.
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发现潜在的预后长非编码RNA生物标志物，用于预测乳腺癌患者肿瘤复发的风险
DOI：
10.1038/srep31038
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发表时间：
2016-08-09
影响因子：
4.6
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Zhou M;Zhong L;Xu W;Sun Y;Zhang Z;Zhao H;Yang L;Sun J
已证明长链非编码RNA（lncRNA）表达的失调参与癌症的发展和进展。然而，lncRNA在乳腺癌复发中的表达模式和预后价值仍不清楚。在这里，我们通过重新利用基因表达综合数据库中现有的微阵列数据集，分析了乳腺癌患者的lncRNA表达谱，这些患者是否复发，并确定了12种与乳腺癌患者肿瘤复发密切相关的差异表达lncRNA。我们基于来自发现队列的12种复发相关lncRNA的表达水平，通过风险评分方法构建了lncRNA焦点分子特征，将患者分为高风险和低风险组，无复发生存率显著不同（HR = 2.72，95%置信区间2.07-3.57; p = 4.8e-13）。12-lncRNA标记在三个独立验证组中的两个中也代表了类似的预后价值。此外，在至少两个队列中，12-lncRNA特征的预后能力与已知的临床预后因素无关。功能分析表明，预测的复发相关lncRNA可能参与已知的乳腺癌相关的生物学过程和途径。我们的研究结果强调了lncRNA作为新的候选生物标志物来识别肿瘤复发高风险乳腺癌患者的潜力。
Deregulation of long non-coding RNAs (lncRNAs) expression has been proven to be involved in the development and progression of cancer. However, expression pattern and prognostic value of lncRNAs in breast cancer recurrence remain unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients who did or did not develop recurrence by repurposing existing microarray datasets from the Gene Expression Omnibus database, and identified 12 differentially expressed lncRNAs that were closely associated with tumor recurrence of breast cancer patients. We constructed a lncRNA-focus molecular signature by the risk scoring method based on the expression levels of 12 relapse-related lncRNAs from the discovery cohort, which classified patients into high-risk and low-risk groups with significantly different recurrence-free survival (HR = 2.72, 95% confidence interval 2.07–3.57; p = 4.8e-13). The 12-lncRNA signature also represented similar prognostic value in two out of three independent validation cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was independent of known clinical prognostic factors in at least two cohorts. Functional analysis suggested that the predicted relapse-related lncRNAs may be involved in known breast cancer-related biological processes and pathways. Our results highlighted the potential of lncRNAs as novel candidate biomarkers to identify breast cancer patients at high risk of tumor recurrence.