College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China.
College of First Clinical Medicine, Weifang Medical University, Weifang 261041, Shandong Province, China.
Gene. 2019 Dec 30;721:144100. doi: 10.1016/j.gene.2019.144100. Epub 2019 Sep 5.
Breast cancer (BRCA) is the most prevalent cancer that threatens female health. A growing body of evidence has demonstrated the non-negligible effects of messenger RNAs (mRNAs) on biological processes involved in cancers; however, there is no definite conclusion regarding the role of mRNAs in predicting the prognosis of BRCA patients.
We systematically screened the mRNA expression landscape and clinical data of samples from the Cancer Genome Atlas (TCGA). Univariate Cox analysis and robust likelihood-based survival analysis were conducted to identify key mRNAs associated with BRCA. Furthermore, risk scores based on multivariate Cox analysis divided the training set into high-risk and low-risk groups. ROC analysis determined the optimal cut-off point for patient classification of risk levels. The prognostic model was additionally validated in the testing set and complete dataset. Finally, we plotted the survival curves for the mRNAs used in our model.
We obtained the original expression data of 13,617 mRNAs from a total of 1088 samples. After comprehensive survival analysis, the four-mRNA (ACSL1, OTUD3, PKD1L2, and WISP1) prognosis risk assessment model was constructed. Furthermore, the area under cure (AUC) was 0.834, indicating that the model was meaningful and reasonable. In each dataset, analysis based on the four-mRNA signature risk score indicated that the survival status of the group with high risk score was worse than that of the group with low risk scores. Patients with strong mRNA expression of OTUD3, PKD1L2, and WISP1 tended to have good prognosis, whereas patients with high ACSL1 expression tended to have poor prognosis.
In summary, we constructed a four-mRNA prognosis risk assessment model for BRCA. The newly developed model offers more possibilities for assessing prognosis and guiding the selection of better treatment strategies for BRCA.
乳腺癌(BRCA)是威胁女性健康的最常见癌症。越来越多的证据表明信使 RNA(mRNA)对癌症相关生物过程具有不可忽视的影响;然而,关于 mRNA 在预测 BRCA 患者预后中的作用尚未得出明确结论。
我们系统地筛选了癌症基因组图谱(TCGA)样本中的 mRNA 表达谱和临床数据。采用单因素 Cox 分析和稳健似然生存分析鉴定与 BRCA 相关的关键 mRNA。此外,基于多因素 Cox 分析的风险评分将训练集分为高风险和低风险组。ROC 分析确定了患者风险水平分类的最佳截断点。该预后模型还在测试集和完整数据集上进行了验证。最后,我们绘制了模型中使用的 mRNA 的生存曲线。
我们从总共 1088 个样本中获得了 13617 个 mRNA 的原始表达数据。经过全面的生存分析,构建了由 4 个 mRNA(ACSL1、OTUD3、PKD1L2 和 WISP1)组成的预后风险评估模型。此外,AUC 为 0.834,表明该模型具有意义和合理性。在每个数据集上,基于四个 mRNA 特征风险评分的分析表明,高风险评分组的生存状态比低风险评分组差。OTUD3、PKD1L2 和 WISP1 表达较强的患者预后较好,而 ACSL1 表达较高的患者预后较差。
综上所述,我们构建了一个用于 BRCA 的四 mRNA 预后风险评估模型。新开发的模型为评估预后和指导 BRCA 更好的治疗策略选择提供了更多可能性。