Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes
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Rong Liu1,2, Wei Zhang1,2, Zhao-Qian Liu1,2, Hong-Hao Zhou1,2
1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, P. R. China
2Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410008, P. R. China
Hong-Hao Zhou, email: [email protected]
Wei Zhang, email: [email protected]
Keywords: breast cancer, distant metastasis-free survival, gene expression profiling, PAM50 subtype
Received: August 27, 2015 Accepted: January 29, 2016 Published: February 27, 2016
To identify PAM50 subtype–specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10−4), luminal A (HR: 3.03, p=7.2×10−5), luminal B (HR: 3.00, p=2.4×10−10) and HER2+ (HR: 5.49, p=9.7×10−10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options.
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