Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets
Background: High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functi...
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sg-ntu-dr.10356-866082020-03-07T11:48:58Z Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets Kuznetsov, Vladimir A. Tang, Zhiqun Ivshina, Anna V. School of Computer Science and Engineering Ovarian Cancer MicroRNA Background: High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functional relationships between microRNAs, the common pathways controlled by the microRNAs and their prognostic and therapeutic significance remain poorly understood. Methods: We investigated the gene expression patterns of microRNAs in the tumors of 582 HG-SOC patients to identify prognosis signatures and pathways controlled by tumor miRNAs. We developed a variable selection and prognostic method, which performs a robust selection of small-sized subsets of the predictive features (e.g., expressed microRNAs) that collectively serves as the biomarkers of cancer risk and progression stratification system, interconnecting these features with common cancer-related pathways. Results: Across different cohorts, our meta-analysis revealed two robust and unbiased miRNA-based prognostic classifiers. Each classifier reproducibly discriminates HG-SOC patients into high-confidence low-, intermediate- or high-prognostic risk subgroups with essentially different 5-year overall survival rates of 51.6-85%, 20-38.1%, and 0-10%, respectively. Significant correlations of the risk subgroup’s stratification with chemotherapy treatment response were observed. We predicted specific target genes involved in nine cancer-related and two oocyte maturation pathways (neurotrophin and progesterone-mediated oocyte maturation), where each gene can be controlled by more than one miRNA species of the distinct miRNA HG-SOC prognostic classifiers. Conclusions: We identified robust and reproducible miRNA-based prognostic subsets of the of HG-SOC classifiers. The miRNAs of these classifiers could control nine oncogenic and two developmental pathways, highlighting common underlying pathologic mechanisms and perspective targets for the further development of a personalized prognosis assay(s) and the development of miRNA-interconnected pathway-centric and multi-agent therapeutic intervention. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2018-07-30T02:27:31Z 2019-12-06T16:25:40Z 2018-07-30T02:27:31Z 2019-12-06T16:25:40Z 2017 Journal Article Kuznetsov, V. A., Tang, Z., & Ivshina, A. V. (2017). Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets. BMC Genomics, 18(6), 692-. https://hdl.handle.net/10356/86608 http://hdl.handle.net/10220/45342 10.1186/s12864-017-4027-5 en BMC Genomics © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated 24 p. application/pdf |
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Ovarian Cancer MicroRNA Kuznetsov, Vladimir A. Tang, Zhiqun Ivshina, Anna V. Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
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Background: High-grade serous ovarian carcinoma (HG-SOC) is the dominant tumor histologic type in epithelial ovarian cancers, exhibiting highly aberrant microRNA expression profiles and diverse pathways that collectively determine the disease aggressiveness and clinical outcomes. However, the functional relationships between microRNAs, the common pathways controlled by the microRNAs and their prognostic and therapeutic significance remain poorly understood. Methods: We investigated the gene expression patterns of microRNAs in the tumors of 582 HG-SOC patients to identify prognosis signatures and pathways controlled by tumor miRNAs. We developed a variable selection and prognostic method, which performs a robust selection of small-sized subsets of the predictive features (e.g., expressed microRNAs) that collectively serves as the biomarkers of cancer risk and progression stratification system, interconnecting these features with common cancer-related pathways. Results: Across different cohorts, our meta-analysis revealed two robust and unbiased miRNA-based prognostic classifiers. Each classifier reproducibly discriminates HG-SOC patients into high-confidence low-, intermediate- or high-prognostic risk subgroups with essentially different 5-year overall survival rates of 51.6-85%, 20-38.1%, and 0-10%, respectively. Significant correlations of the risk subgroup’s stratification with chemotherapy treatment response were observed. We predicted specific target genes involved in nine cancer-related and two oocyte maturation pathways (neurotrophin and progesterone-mediated oocyte maturation), where each gene can be controlled by more than one miRNA species of the distinct miRNA HG-SOC prognostic classifiers. Conclusions: We identified robust and reproducible miRNA-based prognostic subsets of the of HG-SOC classifiers. The miRNAs of these classifiers could control nine oncogenic and two developmental pathways, highlighting common underlying pathologic mechanisms and perspective targets for the further development of a personalized prognosis assay(s) and the development of miRNA-interconnected pathway-centric and multi-agent therapeutic intervention. |
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School of Computer Science and Engineering |
author_facet |
School of Computer Science and Engineering Kuznetsov, Vladimir A. Tang, Zhiqun Ivshina, Anna V. |
format |
Article |
author |
Kuznetsov, Vladimir A. Tang, Zhiqun Ivshina, Anna V. |
author_sort |
Kuznetsov, Vladimir A. |
title |
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
title_short |
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
title_full |
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
title_fullStr |
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
title_full_unstemmed |
Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets |
title_sort |
identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microrna subsets |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/86608 http://hdl.handle.net/10220/45342 |
_version_ |
1681040824131911680 |