Abstract

<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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.</p><p><b>Results:</b> 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, <i>P</i> = 0.001; HR = 4.46, 95% CI, 1.34–14.91, <i>P</i> = 0.015 for integrated signature and mRNA signature, respectively). Results were validated in the validation set (<i>P</i> = 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.</p><p><b>Conclusions:</b> The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients. <i>Clin Cancer Res; 22(7); 1653–62. ©2016 AACR</i>.</p></div>

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