Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer
Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer
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全面的转录组分析揭示了三阴性乳腺癌的多基因特征。
DOI：
10.1158/1078-0432.ccr-15-1555
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发表时间：
2016-04-01
影响因子：
11.5
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
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作者：
Liu, Yi-Rong;Jiang, Yi-Zhou;Shao, Zhi-Ming
目的：通过整合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签名，以促进三阴性乳腺癌（TNBC）患者的个体化治疗。实验设计：我们使用转录组微阵列分析了165个TNBC样本和33对正常乳腺组织。肿瘤特异性mRNA和lncRNA被鉴定并与患者的无复发生存期（RFS）相关。利用考克斯回归模型，我们建立了两个多基因签名纳入mRNA和lncRNA。在165名TNBC患者的训练集中测试了特征的预后和预测准确性，并在其他101名TNBC患者中进行了验证。结果：我们成功地开发了一个mRNA和一个集成的mRNA-lncRNA签名的基础上，八个mRNA和两个lncRNA。在训练集中，在两个签名中，高风险组的患者比低风险组的患者更可能患有复发性疾病[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）。结果在验证集中得到验证（分别为P = 0.019和0.030）。此外，时间依赖性受试者操作曲线显示，在两组中，整合的mRNA-lncRNA标签比仅8个mRNA标签和临床病理风险因素具有更好的预后价值。我们还通过相互作用分析发现，通过整合mRNA-lncRNA标签分类为低风险组的患者对辅助紫杉烷化疗的反应更有利。结论：我们开发的多基因标签可以准确预测TNBC患者的临床结局和紫杉烷化疗的获益。临床癌症研究; 22（7）; 1653-62。©2016 AACR.
Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients. Clin Cancer Res; 22(7); 1653–62. ©2016 AACR.