Please use this identifier to cite or link to this item:
https://doi.org/10.1002/ijc.28371
DC Field | Value | |
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dc.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 | |
dc.contributor.author | Tang, Z. | |
dc.contributor.author | Ow, G.S. | |
dc.contributor.author | Thiery, J.P. | |
dc.contributor.author | Ivshina, A.V. | |
dc.contributor.author | Kuznetsov, V.A. | |
dc.date.accessioned | 2014-12-12T08:01:11Z | |
dc.date.available | 2014-12-12T08:01:11Z | |
dc.date.issued | 2014-01-15 | |
dc.identifier.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 | |
dc.identifier.issn | 00207136 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/117072 | |
dc.description.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. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1002/ijc.28371 | |
dc.source | Scopus | |
dc.subject | cancer biomarker | |
dc.subject | high-grade serous ovarian carcinoma | |
dc.subject | microRNA let-7 | |
dc.subject | survival prognosis | |
dc.subject | tumor classification | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.1002/ijc.28371 | |
dc.description.sourcetitle | International Journal of Cancer | |
dc.description.volume | 134 | |
dc.description.issue | 2 | |
dc.description.page | 306-318 | |
dc.description.coden | IJCNA | |
dc.identifier.isiut | 000326649300058 | |
Appears in Collections: | Staff Publications |
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