Comprehensive transcriptome profiling reveals multigene signatures in triple-negative breast cancer: a prospective observational study and validation
Menée initialement à partir de 165 échantillons de tissu tumoral et 33 échantillons de tissu sain prélevés sur 165 patientes atteintes d'un cancer du sein triplement négatif, puis validée sur 101 patientes complémentaires, cette étude identifie une signature, basée sur l'expression de 8 ARNs messagers et 2 longs ARNs non codants, en association avec la réponse à une chimiothérapie à base de taxane
Purpose: By integrating expression profiles of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs), we tried to develop and validate novel multigene signatures to facilitate individualized treatment of TNBC patients.
Experimental Design: We analysed 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 another 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 high-risk group were more likely to suffer from recurrent disease than patients in low-risk group in both signatures (hazard ratio [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). Additionally, 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 clinicopathological 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 favourable response to adjuvant taxane chemotherapy.
Conclusions: The multigene signature we developed can accurately predict clinical outcome and benefit of taxane chemotherapy in TNBC patients.
Clinical Cancer Research , résumé, 2016