一个由 8 个长链非编码 RNA 组成的panel 可预测乳腺癌患者的预后和乳腺癌细胞的迁移。
A panel of 8-lncRNA predicts prognosis of breast cancer patients and migration of breast cancer cells.
机构信息
Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
出版信息
PLoS One. 2021 Jun 4;16(6):e0249174. doi: 10.1371/journal.pone.0249174. eCollection 2021.
BACKGROUND
Breast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients.
METHODS
Systematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores.
RESULTS
Our study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model.
CONCLUSION
Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa.
背景
乳腺癌（BCa）是全球女性最常见的癌症，也是癌症死亡的主要原因。最近的研究表明，长链非编码 RNA（lncRNA）可以作为许多类型癌症（包括胰腺腺癌、胃癌、肝癌和肺癌）诊断和预后的独立生物标志物。以前的研究表明，许多 lncRNA 与 BCa 的发生和发展有关。然而，很少有研究将多个 lncRNA 结合起来预测早期 BCa 患者的预后。
方法
对来自癌症基因组图谱（TCGA）的数据进行系统和全面的分析，以确定具有 BCa 预后价值的 lncRNA 特征。此外，通过定量实时 PCR（qPCR）检测了几种 BCa 细胞系中 8 种 lncRNA 的相对表达水平，并将结果代入风险评分公式。最后，根据不同风险评分的细胞系中的风险评分，通过迁移实验验证预后分析的结果。
结果
我们的研究纳入了 808 名具有完整临床数据的 BCa 患者。通过 Wilcox 检验鉴定出一组 8 个 lncRNA，这些 lncRNA 在 BCa 患者的正常组织和肿瘤组织之间存在差异。该面板用于分析 BCa 患者的生存情况。低风险评分患者的总生存期（OS）明显长于高风险评分患者。多变量 Cox 回归分析表明，lncRNA 特征是独立的预后因素。基因集富集分析（GSEA）表明，这些 lncRNA 可能参与了与 BCa 相关的几个分子信号通路，如 DNA 复制通路、细胞周期通路和戊糖磷酸通路。在乳腺癌细胞中进行的验证实验通过划痕实验测试细胞迁移，支持了该模型的结果。
结论
本研究表明，一组 8 个 lncRNA 有可能作为 BCa 的独立预后生物标志物。
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