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Title: Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma
Authors: Tang, Zhiqun
Ow, Ghim Siong
Thiery, Jean Paul
Ivshina, Anna V.
Kuznetsov, Vladimir A.
Keywords: High-grade serous ovarian carcinoma
MicroRNA let-7
Issue Date: 2014
Source: Tang, Z., Ow, G. S., Thiery, J. P., Ivshina, A. V., & Kuznetsov, V. A. (2014). Meta-analysis of transcriptome reveals let-7b as an unfavorable prognostic biomarker and predicts molecular and clinical subclasses in high-grade serous ovarian carcinoma. International Journal of Cancer, 134(2), 306-318.
Series/Report no.: International Journal of Cancer
Abstract: High-grade serous ovarian carcinoma (HG-SOC) is a heterogeneous, poorly classified, lethal disease that frequently exhibits altered expressions of microRNAs. Let-7 family members are often reported as tumor suppressors; nonetheless, clinicopathological functions and prognostic values of individual let-7 family members have not been addressed in HG-SOC. In our work, we performed an integrative study to investigate the potential roles, clinicopathological functions and prognostic values of let-7 miRNA family in HG-SOC. Using microarray and clinical data of 1,170 HG-SOC patients, we developed novel survival prediction and system biology methods to analyze prognostic values and functional associations of let-7 miRNAs with global transcriptome and clinicopathological factors. We demonstrated that individual let-7 members exhibit diverse evolutionary history and distinct regulatory characteristics. Statistical tests and network analysis suggest that let-7b could act as a global synergistic interactor and master regulator controlling hundreds of protein-coding genes. The elevated expression of let-7b is associated with poor survival rates, which suggests an unfavorable role of let-7b in treatment response for HG-SOC patients. A novel let-7b-defined 36-gene prognostic survival signature outperforms many clinicopathological parameters, and stratifies HG-SOC patients into three high-confidence, reproducible, clinical subclasses: low-, intermediate- and high-risk, with 5-year overall survival rates of 56–71%, 12–29% and 0–10%, respectively. Furthermore, the high-risk and low-risk subclasses exhibit strong mesenchymal and proliferative tumor phenotypes concordant with resistance and sensitivity to primary chemotherapy. Our results have led to identification of promising prognostic markers of HG-SOC, which could provide a rationale for genetic-based stratification of patients and optimization of treatment regimes.
ISSN: 0020-7136
DOI: 10.1002/ijc.28371
Schools: School of Computer Engineering 
Rights: © 2013 UICC.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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