PT  - JOURNAL ARTICLE
AU  - Liu, Yi-Rong
AU  - Jiang, Yi-Zhou
AU  - Xu, Xiao-En
AU  - Hu, Xin
AU  - Yu, Ke-Da
AU  - Shao, Zhi-Ming
TI  - Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer
AID  - 10.1158/1078-0432.CCR-15-1555
DP  - 2016 Apr 01
TA  - Clinical Cancer Research
PG  - 1653--1662
VI  - 22
IP  - 7
4099  - http://clincancerres.aacrjournals.org/content/22/7/1653.short
4100  - http://clincancerres.aacrjournals.org/content/22/7/1653.full
SO  - Clin Cancer Res2016 Apr 01; 22
AB  - 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.