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https://doi.org/10.1002/ijc.28371
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. https://doi.org/10.1002/ijc.28371 | 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 | URI: | http://scholarbank.nus.edu.sg/handle/10635/117072 | ISSN: | 00207136 | DOI: | 10.1002/ijc.28371 |
Appears in Collections: | Staff Publications |
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