Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China. Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China.
Clin Cancer Res. 2016 Apr 1;22(7):1653-62. doi: 10.1158/1078-0432.CCR-15-1555. Epub 2016 Jan 26.
By integrating expression profiles of mRNAs and long noncoding RNAs (lncRNA), we tried to develop and validate novel multigene signatures to facilitate individualized treatment of triple-negative breast cancer (TNBC) patients.
We analyzed 165 TNBC samples and 33 paired normal breast tissues using transcriptome microarrays. Tumor-specific mRNAs and lncRNAs were identified and correlated with patients' recurrence-free survival (RFS). Using Cox regression model, we built two multigene signatures incorporating mRNAs and lncRNAs. The prognostic and predictive accuracy of the signatures were tested in a training set of 165 TNBC patients and validated in other 101 TNBC patients.
We successfully developed an mRNA and an integrated mRNA-lncRNA signature based on eight mRNAs and two lncRNAs. In the training set, patients in the high-risk group were more likely to suffer from recurrent disease than patients in the low-risk group in both signatures [HR, 10.00; 95% confidence interval (CI), 2.53-39.47, P= 0.001; HR = 4.46, 95% CI, 1.34-14.91, P= 0.015 for integrated signature and mRNA signature, respectively). Results were validated in the validation set (P= 0.019 and 0.030, respectively). In addition, time-dependent receiver operating curve showed that the integrated mRNA-lncRNA signature had a better prognostic value than both the eight-mRNA-only signature and the clinicopathologic risk factors in both sets. We also found through interaction analysis that patients classified into the low-risk group by the integrated mRNA-lncRNA signature had a more favorable response to adjuvant taxane chemotherapy.
The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients.
通过整合信使 RNA（mRNA）和长链非编码 RNA（lncRNA）的表达谱，我们试图开发和验证新的多基因标志物，以促进三阴性乳腺癌（TNBC）患者的个体化治疗。
我们使用转录组微阵列分析了 165 例 TNBC 样本和 33 对配对的正常乳腺组织。鉴定了肿瘤特异性的 mRNAs 和 lncRNAs，并与患者的无复发生存率（RFS）相关。使用 Cox 回归模型，我们构建了两个包含 mRNAs 和 lncRNAs 的多基因标志物。在 165 例 TNBC 患者的训练集中测试了这些标志物的预后和预测准确性，并在另外 101 例 TNBC 患者中进行了验证。
我们成功地基于 8 个 mRNAs 和 2 个 lncRNAs 开发了一个 mRNA 和一个整合的 mRNA-lncRNA 标志物。在训练集中，高风险组的患者比低风险组的患者更容易发生复发病例[风险比（HR），10.00；95%置信区间（CI），2.53-39.47，P=0.001；HR=4.46，95%CI，1.34-14.91，P=0.015，分别为整合标志物和 mRNA 标志物]。结果在验证集中得到了验证（分别为 P=0.019 和 0.030）。此外，时间依赖性接收者操作曲线显示，整合的 mRNA-lncRNA 标志物在两个数据集的预后价值均优于仅包含 8 个 mRNA 的标志物和临床病理危险因素。通过交互分析，我们还发现，通过整合的 mRNA-lncRNA 标志物分类为低风险组的患者对辅助紫杉烷化疗有更好的反应。
我们开发的多基因标志物可以准确预测 TNBC 患者的临床结局和紫杉烷化疗的获益。
