Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer

Douglas C Marchion; Yin Xiong; Hye Sook Chon; Entidhar Al Sawah; Nadim Bou Zgheib; Ingrid J Ramirez; Forough Abbasi; Xiaomang B Stickles; Patricia L Judson; Ardeshir Hakam; Jesus Gonzalez-Bosquet; Robert M Wenham; Sachin M Apte; Anders E Berglund; Johnathan M Lancaster

doi:10.1016/j.ajog.2013.08.004

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Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer

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Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer

Douglas C Marchion, Yin Xiong, Hye Sook Chon, Entidhar Al Sawah, Nadim Bou Zgheib, Ingrid J Ramirez, Forough Abbasi, Xiaomang B Stickles, Patricia L Judson, Ardeshir Hakam, …

American Journal of Obstetrics and Gynecology, Vol.209(6), pp.576.e1-576.e16

12/2013

DOI: 10.1016/j.ajog.2013.08.004

PMCID: PMC3840156

PMID: 23933223

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Abstract

The objective of the study was to evaluate the biological validity of ovarian cancer (OVCA) screening and early detection efforts and to characterize signaling pathways associated with human cancer metastasis and patient survival. Using genome-wide expression profiling and deoxyribonucleic acid sequencing, we compared pelvic and matched extrapelvic implants from 30 patients with advanced-stage OVCA for expression of molecular signaling pathways and p53 gene mutations. Differentially expressed pathways were further evaluated in a series of primary or early-stage vs metastatic or recurrent cancer samples from 389 ovarian, prostate, and oral cancer patients. Metastasis pathways were also evaluated for associations with survival in 9 independent clinicogenomic datasets from 1691 ovarian, breast, colon, brain, and lung cancer and leukemia patients. The inhibitory effects of 1 pathway (transforming growth factor [TGF]-WNT) on in vitro OVCA cell migration were studied. Pelvic and extrapelvic OVCA implants demonstrated similar patterns of signaling pathway expression and identical p53 mutations. However, we identified 3 molecular pathways/cellular processes that were differentially expressed between pelvic and extrapelvic OVCA samples and between primary/early-stage and metastatic/advanced or recurrent ovarian, oral, and prostate cancers. Furthermore, their expression was associated with overall survival from ovarian cancer (P = .006), colon cancer (1 pathway at P = .005), and leukemia (P = .05). Artesunate-induced TGF-WNT pathway inhibition impaired OVCA cell migration. Advanced-stage OVCA has a unifocal origin in the pelvis. Molecular pathways associated with extrapelvic OVCA spread are also associated with metastasis from other human cancers and with overall patient survival. Such pathways represent appealing therapeutic targets for patients with metastatic disease.

Gene Expression

unifocal

serous ovarian cancer

p53 mutation

Details

Title: Subtitle: Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer
Creators: Douglas C Marchion - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Yin Xiong - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Hye Sook Chon - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Entidhar Al Sawah - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Nadim Bou Zgheib - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Ingrid J Ramirez - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Forough Abbasi - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Xiaomang B Stickles - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Patricia L Judson - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Ardeshir Hakam - Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Jesus Gonzalez-Bosquet - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Robert M Wenham - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Sachin M Apte - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Anders E Berglund - Department of Biomedical Informatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Johnathan M Lancaster - Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Resource Type: Journal article
Publication Details: American Journal of Obstetrics and Gynecology, Vol.209(6), pp.576.e1-576.e16
DOI: 10.1016/j.ajog.2013.08.004
PMID: 23933223
PMCID: PMC3840156
NLM abbreviation: Am J Obstet Gynecol
ISSN: 0002-9378
eISSN: 1097-6868
Publisher: Mosby, Inc
Grant note: Palm Healthcare Foundation H.O.W. 2 P30-CA76292-14 / National Cancer Institute Jacquie Liggett Fellowship National Institutes of Health Hearing the Ovarian Cancer Whisper
Language: English
Date published: 12/2013
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983931739302771

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