Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer
Yi-Rong Liu1,2,3, Yi-Zhou Jiang1,2,3, Xiao-En Xu1,2,3, Xin Hu1,2,3, Ke-Da Yu1,2,3, and Zhi-Ming Shao1,2,3,4,*
1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
2Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
4Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China.
Zhi-Ming Shao, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, 270 Dong-An Road, Shanghai, 200032, P.R. China. Phone: +86-21-64175590; Fax: +86-21-64438653; Email: email@example.com; and Ke-Da Yu, firstname.lastname@example.org
Y.-R. Liu, Y.-Z. Jiang, and X.-E. Xu contributed equally to this article; K.-D. Yu and Z.-M. Shao contributed equally to this article.
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.
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