Format

Send to

Choose Destination
Clin Cancer Res. 2016 Apr 1;22(7):1653-62. doi: 10.1158/1078-0432.CCR-15-1555. Epub 2016 Jan 26.

Comprehensive Transcriptome Profiling Reveals Multigene Signatures in Triple-Negative Breast Cancer.

Author information

1
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
2
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China. zhimingshao@yahoo.com yukeda@163.com.
3
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, P.R. China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China. Institutes of Biomedical Sciences, Fudan University, Shanghai, P.R. China. zhimingshao@yahoo.com yukeda@163.com.

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.

PMID:
26813360
DOI:
10.1158/1078-0432.CCR-15-1555
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center