Bluewater Biotech LLC, PO Box 1010, New Providence, NJ, 07974, USA.
Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Breast Cancer Res Treat. 2020 Aug;183(1):95-105. doi: 10.1007/s10549-020-05770-8. Epub 2020 Jun 29.
The development of multi-gene signatures has led to improvements in identification of breast cancer patients at high risk of recurrence. The prognostic power of commercially available gene signatures is mostly restricted to estrogen receptor (ER)-positive breast cancer. On the contrary, immune-related gene signatures predict prognosis only in ER-negative breast cancer. This study aimed to develop a better prognostic signature for breast cancer.
The expressions of long non-coding RNA (lncRNA) genes from 30 independent microarray datasets with a total of 4813 samples were analyzed. A prognostic lncRNA signature was developed based on likelihood-ratio Cox regression analysis. Survival analysis was used to compare the prognostic efficiencies of our signature and 10 previously reported prognostic gene signatures.
Cox regression analysis on 30 independent datasets showed that the 6-lncRNA signature identified in this study performed as well as five commercially available signatures in recurrence prediction for ER-positive breast cancer. In ER-negative breast cancer, this lncRNA signature was as prognostic as three immune-related gene signatures. Moreover, our lncRNA signature also demonstrated a good capacity to predict recurrence risk for triple-negative breast cancer. Function analysis showed that several lncRNAs in this signature were probably involved in cell proliferation and immune processes.
A six-LncRNA signature was identified that is prognostic for ER-positive, ER-negative, and triple-negative breast cancers and thus deserves further validation in prospective studies.
多基因标志物的发展提高了对高复发风险乳腺癌患者的识别能力。商业上可用的基因标志物的预后能力主要局限于雌激素受体（ER）阳性乳腺癌。相反，与免疫相关的基因标志物仅在 ER 阴性乳腺癌中预测预后。本研究旨在开发一种更好的乳腺癌预后标志物。
分析了来自 30 个独立微阵列数据集的长链非编码 RNA（lncRNA）基因的表达，总共有 4813 个样本。基于似然比 Cox 回归分析，开发了一种预后 lncRNA 标志物。生存分析用于比较我们的标志物和 10 个先前报道的预后基因标志物的预后效率。
对 30 个独立数据集的 Cox 回归分析表明，本研究中确定的 6-lncRNA 标志物在 ER 阳性乳腺癌的复发预测中与五个商业上可用的标志物表现一样好。在 ER 阴性乳腺癌中，这种 lncRNA 标志物与三个与免疫相关的基因标志物一样具有预后能力。此外，我们的 lncRNA 标志物也显示出预测三阴性乳腺癌复发风险的良好能力。功能分析表明，该标志物中的几个 lncRNA 可能参与细胞增殖和免疫过程。
确定了一个六 lncRNA 标志物，可用于预测 ER 阳性、ER 阴性和三阴性乳腺癌的预后，因此值得在前瞻性研究中进一步验证。
