Yi-Rong Liu^1,2,3, Yi-Zhou Jiang^1,2,3, Xiao-En Xu^1,2,3, Xin Hu^1,2,3, Ke-Da Yu^1,2,3, and Zhi-Ming Shao^1,2,3,4,*

Author Affiliations

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.

↵*Corresponding Author:
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: zhimingshao@yahoo.com; and Ke-Da Yu, yukeda@163.com   

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.

Abstract

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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