A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer
Abstract
The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan–Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics studymore »
- Authors:
-
[7];
[6]
- Nanjing Medical Univ. (China); Peking Univ. Third Hospital, Beijing (China)
- Peking Univ. Health Science Center, Beijing (China)
- Beijing Maternal and Child Health Care Hospital (China)
- The Third Affiliated Hospital of Chongqing Medical Univ., Chongqing (China)
- Nanjing Univ. Medical School, Jiangsu (China)
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Peking Univ. Third Hospital, Beijing (China)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Key Research and Development Program for Reproductive Health and Major Birth Defects Control and Prevention; China Scholarship Council
- OSTI Identifier:
- 1599791
- Grant/Contract Number:
- AC02-05CH11231; 2017YFC1002004; 201606010313
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Oncology
- Additional Journal Information:
- Journal Volume: 2019; Journal ID: ISSN 1687-8450
- Publisher:
- Hindawi
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Zhao, Yue, Yang, Shao-Min, Jin, Yu-Lan, Xiong, Guang-Wu, Wang, Pin, Snijders, Antoine M., Mao, Jian-Hua, Zhang, Xiao-Wei, and Hang, Bo. A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer. United States: N. p., 2019.
Web. doi:10.1155/2019/3614207.
Zhao, Yue, Yang, Shao-Min, Jin, Yu-Lan, Xiong, Guang-Wu, Wang, Pin, Snijders, Antoine M., Mao, Jian-Hua, Zhang, Xiao-Wei, & Hang, Bo. A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer. United States. https://doi.org/10.1155/2019/3614207
Zhao, Yue, Yang, Shao-Min, Jin, Yu-Lan, Xiong, Guang-Wu, Wang, Pin, Snijders, Antoine M., Mao, Jian-Hua, Zhang, Xiao-Wei, and Hang, Bo. Thu .
"A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer". United States. https://doi.org/10.1155/2019/3614207. https://www.osti.gov/servlets/purl/1599791.
@article{osti_1599791,
title = {A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer},
author = {Zhao, Yue and Yang, Shao-Min and Jin, Yu-Lan and Xiong, Guang-Wu and Wang, Pin and Snijders, Antoine M. and Mao, Jian-Hua and Zhang, Xiao-Wei and Hang, Bo},
abstractNote = {The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan–Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics study combining transcriptomic and clinical data established an 11-gene prognostic signature for robust and reproducible prediction of OS in HGSOC patients. This signature could be of clinical value for guiding therapeutic selection and individualized treatment.},
doi = {10.1155/2019/3614207},
journal = {Journal of Oncology},
number = ,
volume = 2019,
place = {United States},
year = {Thu Nov 07 00:00:00 EST 2019},
month = {Thu Nov 07 00:00:00 EST 2019}
}
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Works referenced in this record:
Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
journal, December 2013
- Győrffy, Balázs; Surowiak, Pawel; Budczies, Jan
- PLoS ONE, Vol. 8, Issue 12
Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer
journal, January 2018
- Zhan, Xiao-Yong; Zhang, Yaqiong; Zhai, Ertao
- PeerJ, Vol. 6
MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion
journal, January 2018
- Lin, Hao ; Huang, Bin; Wang, Hua
- Cellular Physiology and Biochemistry, Vol. 51, Issue 2
Integrin Subunit beta 8 (ITGB8) Upregulation Is an Independent Predictor of Unfavorable Survival of High-Grade Serous Ovarian Carcinoma Patients
journal, January 2018
- He, Jing; Liu, Yan; Zhang, Lixia
- Medical Science Monitor, Vol. 24
A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
journal, July 2008
- Bonome, T.; Levine, D. A.; Shih, J.
- Cancer Research, Vol. 68, Issue 13
Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis
journal, December 2006
- Nguyen, L. N.; Holdren, M. S.; Nguyen, A. P.
- Clinical Cancer Research, Vol. 12, Issue 23
Integrative network analysis of TCGA data for ovarian cancer
journal, December 2014
- Zhang, Qingyang; Burdette, Joanna E.; Wang, Ji-Ping
- BMC Systems Biology, Vol. 8, Issue 1
Expression of Tumor-rejection Antigens in Gynecologic Cancers
journal, November 2000
- Tanaka, Shoko; Tsuda, Naotake; Kawano, Kouichirou
- Japanese Journal of Cancer Research, Vol. 91, Issue 11
Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study
journal, February 2018
- Lee, Jung-Min; Nair, Jayakumar; Zimmer, Alexandra
- The Lancet Oncology, Vol. 19, Issue 2
Prognostic and Therapeutic Relevance of Molecular Subtypes in High-Grade Serous Ovarian Cancer
journal, September 2014
- Konecny, Gottfried E.; Wang, Chen; Hamidi, Habib
- JNCI: Journal of the National Cancer Institute, Vol. 106, Issue 10
Identification of cancer biomarkers of prognostic value using specific gene regulatory networks (GRN): a novel role of RAD51AP1 for ovarian and lung cancers
journal, November 2017
- Chudasama, Dimple; Bo, Valeria; Hall, Marcia
- Carcinogenesis, Vol. 39, Issue 3
Integrins and Cell Metabolism: An Intimate Relationship Impacting Cancer
journal, January 2017
- Ata, Rehman; Antonescu, Costin
- International Journal of Molecular Sciences, Vol. 18, Issue 1
Pathogenesis and heterogeneity of ovarian cancer
journal, January 2017
- Kroeger, Paul T.; Drapkin, Ronny
- Current Opinion in Obstetrics and Gynecology, Vol. 29, Issue 1
ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks
journal, February 2009
- Bindea, Gabriela; Mlecnik, Bernhard; Hackl, Hubert
- Bioinformatics, Vol. 25, Issue 8
Prognostic role of N-Acetylgalactosaminyltransferase 10 in metastatic renal cell carcinoma
journal, January 2017
- Liu, Li; Xiong, Ying; Xi, Wei
- Oncotarget, Vol. 8, Issue 9
New insights into ovarian cancer pathology
journal, September 2012
- Prat, J.
- Annals of Oncology, Vol. 23
A robust gene expression-based prognostic risk score predicts overall survival of lung adenocarcinoma patients
journal, December 2017
- Chen, En-Guo; Wang, Pin; Lou, Haizhou
- Oncotarget, Vol. 9, Issue 6
Ovarian Low-grade and High-grade Serous Carcinoma: Pathogenesis, Clinicopathologic and Molecular Biologic Features, and Diagnostic Problems
journal, January 2009
- Vang, Russell; Shih, Ie-Ming; Kurman, Robert J.
- Advances in Anatomic Pathology, Vol. 16, Issue 5
Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients
journal, January 2012
- Győrffy, Balázs; Lánczky, András; Szállási, Zoltán
- Endocrine-Related Cancer, Vol. 19, Issue 2
The mitochondrial one‑carbon metabolic pathway is associated with patient survival in pancreatic cancer
journal, May 2018
- Noguchi, Kozo; Konno, Masamitsu; Koseki, Jun
- Oncology Letters
Ovarian cancer
journal, August 2016
- Matulonis, Ursula A.; Sood, Anil K.; Fallowfield, Lesley
- Nature Reviews Disease Primers, Vol. 2, Issue 1
DyNet: visualization and analysis of dynamic molecular interaction networks
journal, May 2016
- Goenawan, Ivan H.; Bryan, Kenneth; Lynn, David J.
- Bioinformatics, Vol. 32, Issue 17
Epidemiology of ovarian cancer: a review
journal, January 2017
- Brett M., Reid; Jennifer B., Permuth; Thomas A., Sellers
- Cancer Biology & Medicine, Vol. 14, Issue 1
Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Outcome
journal, August 2008
- Tothill, R. W.; Tinker, A. V.; George, J.
- Clinical Cancer Research, Vol. 14, Issue 16
Validation of ovarian cancer gene expression signatures for survival and subtype in formalin fixed paraffin embedded tissues
journal, April 2013
- Sfakianos, Gregory P.; Iversen, Edwin S.; Whitaker, Regina
- Gynecologic Oncology, Vol. 129, Issue 1
Meta- and Orthogonal Integration of Influenza “OMICs” Data Defines a Role for UBR4 in Virus Budding
journal, December 2015
- Tripathi, Shashank; Pohl, Marie O.; Zhou, Yingyao
- Cell Host & Microbe, Vol. 18, Issue 6
Integrated genomic analyses of ovarian carcinoma
journal, June 2011
- Network, Atlas Research
- Nature, Vol. 474, Issue 7353, p. 609-615
Cancer statistics, 2017
journal, January 2017
- Siegel, Rebecca L.; Miller, Kimberly D.; Jemal, Ahmedin
- CA: A Cancer Journal for Clinicians, Vol. 67, Issue 1
A Five-Gene Expression Signature Predicts Clinical Outcome of Ovarian Serous Cystadenocarcinoma
journal, January 2016
- Liu, Li-Wei; Zhang, Qiuhao; Guo, Wenna
- BioMed Research International, Vol. 2016
Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis
journal, January 2018
- Koseki, Jun; Konno, Masamitsu; Asai, Ayumu
- Scientific Reports, Vol. 8, Issue 1
A novel gene expression-based prognostic scoring system to predict survival in gastric cancer
journal, July 2016
- Wang, Pin; Wang, Yunshan; Hang, Bo
- Oncotarget, Vol. 7, Issue 34
A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies
journal, March 2012
- Kratz, Johannes R.; He, Jianxing; Van Den Eeden, Stephen K.
- The Lancet, Vol. 379, Issue 9818
DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling
journal, June 2018
- Liao, Wen-Chieh; Liao, Chih-Kai; Tsai, You-Huan
- PLOS ONE, Vol. 13, Issue 6
Identification of Genes With Differential Expression in Chemoresistant Epithelial Ovarian Cancer Using High-Density Oligonucleotide Microarrays
journal, February 2009
- Ju, Woong; Yoo, Byong Chul; Kim, Il-Jin
- Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Vol. 18, Issue 2
Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer
journal, August 2020
- Kim, Ji-Yeon; Jung, Hae Hyun; Sohn, Insuk
- Breast Cancer Research and Treatment, Vol. 184, Issue 2
Thermal stress induces glycolytic beige fat formation via a myogenic state
journal, December 2018
- Chen, Yong; Ikeda, Kenji; Yoneshiro, Takeshi
- Nature, Vol. 565, Issue 7738
Integrated genomic analyses of ovarian carcinoma
text, January 2011
- Charles, Perou,
- The University of North Carolina at Chapel Hill University Libraries
Ovarian Cancer: Histogenetic Classification, Histologic Grading, Diagnosis, Staging, and Epidemiology
journal, January 1985
- Jolles, Christopher J.
- Clinical Obstetrics and Gynecology, Vol. 28, Issue 4
Validation of ovarian cancer gene expression signatures for survival and subtype in formalin fixed paraffin embedded tissues
journal, April 2013
- Sfakianos, Gregory P.; Iversen, Edwin S.; Whitaker, Regina
- Gynecologic Oncology, Vol. 129, Issue 1
A practical molecular assay to predict survival in resected non-squamous, non-small-cell lung cancer: development and international validation studies
journal, March 2012
- Kratz, Johannes R.; He, Jianxing; Van Den Eeden, Stephen K.
- The Lancet, Vol. 379, Issue 9818
Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study
journal, February 2018
- Lee, Jung-Min; Nair, Jayakumar; Zimmer, Alexandra
- The Lancet Oncology, Vol. 19, Issue 2
Integrated genomic analyses of ovarian carcinoma
journal, June 2011
- Network, Atlas Research
- Nature, Vol. 474, Issue 7353, p. 609-615
Ovarian cancer
journal, August 2016
- Matulonis, Ursula A.; Sood, Anil K.; Fallowfield, Lesley
- Nature Reviews Disease Primers, Vol. 2, Issue 1
Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis
journal, January 2018
- Koseki, Jun; Konno, Masamitsu; Asai, Ayumu
- Scientific Reports, Vol. 8, Issue 1
Diagnostic classification of cancers using DNA methylation of paracancerous tissues
journal, June 2022
- Ma, Baoshan; Chai, Bingjie; Dong, Heng
- Scientific Reports, Vol. 12, Issue 1
New insights into ovarian cancer pathology
journal, September 2012
- Prat, J.
- Annals of Oncology, Vol. 23
DyNet: visualization and analysis of dynamic molecular interaction networks
journal, May 2016
- Goenawan, Ivan H.; Bryan, Kenneth; Lynn, David J.
- Bioinformatics, Vol. 32, Issue 17
Identification of cancer biomarkers of prognostic value using specific gene regulatory networks (GRN): a novel role of RAD51AP1 for ovarian and lung cancers
journal, November 2017
- Chudasama, Dimple; Bo, Valeria; Hall, Marcia
- Carcinogenesis, Vol. 39, Issue 3
Pathogenesis and heterogeneity of ovarian cancer
journal, January 2017
- Kroeger, Paul T.; Drapkin, Ronny
- Current Opinion in Obstetrics and Gynecology, Vol. 29, Issue 1
Expression of Tumor-rejection Antigens in Gynecologic Cancers
journal, November 2000
- Tanaka, Shoko; Tsuda, Naotake; Kawano, Kouichirou
- Japanese Journal of Cancer Research, Vol. 91, Issue 11
A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
journal, July 2008
- Bonome, T.; Levine, D. A.; Shih, J.
- Cancer Research, Vol. 68, Issue 13
Sorting Nexin 1 Down-Regulation Promotes Colon Tumorigenesis
journal, December 2006
- Nguyen, L. N.; Holdren, M. S.; Nguyen, A. P.
- Clinical Cancer Research, Vol. 12, Issue 23
MTHFD2 Overexpression Predicts Poor Prognosis in Renal Cell Carcinoma and is Associated with Cell Proliferation and Vimentin-Modulated Migration and Invasion
journal, January 2018
- Lin, Hao ; Huang, Bin; Wang, Hua
- Cellular Physiology and Biochemistry, Vol. 51, Issue 2
Integrative network analysis of TCGA data for ovarian cancer
journal, December 2014
- Zhang, Qingyang; Burdette, Joanna E.; Wang, Ji-Ping
- BMC Systems Biology, Vol. 8, Issue 1
Integrin Subunit beta 8 (ITGB8) Upregulation Is an Independent Predictor of Unfavorable Survival of High-Grade Serous Ovarian Carcinoma Patients
journal, January 2018
- He, Jing; Liu, Yan; Zhang, Lixia
- Medical Science Monitor, Vol. 24
DSE promotes aggressive glioma cell phenotypes by enhancing HB-EGF/ErbB signaling
journal, June 2018
- Liao, Wen-Chieh; Liao, Chih-Kai; Tsai, You-Huan
- PLOS ONE, Vol. 13, Issue 6
Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients
journal, January 2012
- Győrffy, Balázs; Lánczky, András; Szállási, Zoltán
- Endocrine-Related Cancer, Vol. 19, Issue 2
A novel gene expression-based prognostic scoring system to predict survival in gastric cancer
journal, July 2016
- Wang, Pin; Wang, Yunshan; Hang, Bo
- Oncotarget, Vol. 7, Issue 34
Prognostic role of N-Acetylgalactosaminyltransferase 10 in metastatic renal cell carcinoma
journal, January 2017
- Liu, Li; Xiong, Ying; Xi, Wei
- Oncotarget, Vol. 8, Issue 9
Epidemiology of ovarian cancer: a review
journal, January 2017
- Brett M., Reid; Jennifer B., Permuth; Thomas A., Sellers
- Cancer Biology & Medicine, Vol. 14, Issue 1
Identification of Genes With Differential Expression in Chemoresistant Epithelial Ovarian Cancer Using High-Density Oligonucleotide Microarrays
journal, February 2009
- Ju, Woong; Yoo, Byong Chul; Kim, Il-Jin
- Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Vol. 18, Issue 2
Sorting nexin-1 is a candidate tumor suppressor and potential prognostic marker in gastric cancer
journal, January 2018
- Zhan, Xiao-Yong; Zhang, Yaqiong; Zhai, Ertao
- PeerJ, Vol. 6