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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, Z.
Ow, G.S.
Thiery, J.P. 
Ivshina, A.V.
Kuznetsov, V.A.
Keywords: cancer biomarker
high-grade serous ovarian carcinoma
microRNA let-7
survival prognosis
tumor classification
Issue Date: 15-Jan-2014
Citation: Tang, Z., Ow, G.S., Thiery, J.P., Ivshina, A.V., Kuznetsov, V.A. (2014-01-15). 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. ScholarBank@NUS Repository.
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. © 2013 UICC.
Source Title: International Journal of Cancer
ISSN: 00207136
DOI: 10.1002/ijc.28371
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