Oncotarget

Research Papers:

The 3′UTR signature defines a highly metastatic subgroup of triple-negative breast cancer

Lei Wang, Xin Hu, Peng Wang and Zhi-Ming Shao _

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Oncotarget. 2016; 7:59834-59844. https://doi.org/10.18632/oncotarget.10975

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Abstract

Lei Wang1,2,3, Xin Hu1,2,3, Peng Wang4,5, Zhi-Ming Shao1,2,3,6

1Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China

2Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China

3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

4Key Laboratory of Systems Biology, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China

5School of Life Science and Technology, ShanghaiTech University, Shanghai, China

6Institutes of Biomedical Sciences, Fudan University, Shanghai, China

Corresponding to:

Zhi-Ming Shao, email: zhimingshao@yahoo.com

Peng Wang, email: wangpeng@sari.ac.cn

Xin Hu, email: xinhu@fudan.edu.cn

Keywords: prognostic modeling, 3′ untranslated region, alternative polyadenylation, triple-negative breast cancer, biomarker

Received: February 6, 2016    Accepted: July 18, 2016    Published: August 01, 2016

ABSTRACT

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with an aggressive clinical course. Prognostic models are needed to chart potential patient outcomes. To address this, we used alternative 3′UTR patterns to improve postoperative risk stratification. We collected 327 publicly available microarrays and generated the 3′UTR landscape based on expression ratios of alternative 3′UTR. After initial feature filtering, we built a 17-3′UTR-based classifier using an elastic net model. Time-dependent ROC comparisons and Kaplan–Meier analyses confirmed an outstanding discriminating power of our prognostic model for TNBC patients. In the training cohort, 5-year event-free survival (EFS) was 78.6% (95% CI 71.2–86.0) for the low-risk group, and 16.3% (95% CI 2.3–30.4) for the high-risk group (log-rank p<0.0001; hazard ratio [HR] 8.29, 95% CI 4.78–14.4), In the validation set, 5-year EFS was 75.6% (95% CI 68.0–83.2) for the low-risk group, and 33.2% (95% CI 17.1–49.3) for the high-risk group (log-rank p<0.0001; HR 3.17, 95% CI 1.66–5.42). In conclusion, the 17-3′UTR-based classifier provides a superior prognostic performance for estimating disease recurrence and metastasis in TNBC patients and it may permit personalized management strategies.


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