Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma

Abstract Background High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC) with poor prognosis. In most cases EOC is widely disseminated at the time of diagnosis. Despite the optimal cytoreductive surgery and chemotherapy most patients develop chem...

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Main Authors: H. Sallinen, S. Janhonen, P. Pölönen, H. Niskanen, O. H. Liu, A. Kivelä, J. M. Hartikainen, M. Anttila, M. Heinäniemi, S. Ylä-Herttuala, M. U. Kaikkonen
Format: Article
Language:English
Published: BMC 2019-11-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-019-6339-0
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author H. Sallinen
S. Janhonen
P. Pölönen
H. Niskanen
O. H. Liu
A. Kivelä
J. M. Hartikainen
M. Anttila
M. Heinäniemi
S. Ylä-Herttuala
M. U. Kaikkonen
author_facet H. Sallinen
S. Janhonen
P. Pölönen
H. Niskanen
O. H. Liu
A. Kivelä
J. M. Hartikainen
M. Anttila
M. Heinäniemi
S. Ylä-Herttuala
M. U. Kaikkonen
author_sort H. Sallinen
collection DOAJ
description Abstract Background High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC) with poor prognosis. In most cases EOC is widely disseminated at the time of diagnosis. Despite the optimal cytoreductive surgery and chemotherapy most patients develop chemoresistance, and the 5-year overall survival being only 25–35%. Methods Here we analyzed the gene expression profiles of 10 primary HGSOC tumors and 10 related omental metastases using RNA sequencing and identified 100 differentially expressed genes. Results The differentially expressed genes were associated with decreased embryogenesis and vasculogenesis and increased cellular proliferation and organismal death. Top upstream regulators responsible for this gene signature were NR5A1, GATA4, FOXL2, TP53 and BMP7. A subset of these genes were highly expressed in the ovarian cancer among the cancer transcriptomes of The Cancer Genome Atlas. Importantly, the metastatic gene signature was suggestive of poor survival in TCGA data based on gene enrichment analysis. Conclusion By comparing the gene expression profiles of primary HGSOC tumors and their matched metastasis, we provide evidence that a signature of 100 genes is able to separate these two sample types and potentially predict patient survival. Our study identifies functional categories of genes and transcription factors that could play important roles in promoting metastases and serve as markers for cancer prognosis.
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spelling doaj.art-23d2fd5ddaae4e6cb92fdda372490d3a2022-12-21T19:17:21ZengBMCBMC Cancer1471-24072019-11-0119111110.1186/s12885-019-6339-0Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinomaH. Sallinen0S. Janhonen1P. Pölönen2H. Niskanen3O. H. Liu4A. Kivelä5J. M. Hartikainen6M. Anttila7M. Heinäniemi8S. Ylä-Herttuala9M. U. Kaikkonen10Department of Obstetrics and Gynecology, Kuopio University HospitalDepartment of Obstetrics and Gynecology, Kuopio University HospitalInstitute of Biomedicine, School of Medicine, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandInstitute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern FinlandDepartment of Obstetrics and Gynecology, Kuopio University HospitalInstitute of Biomedicine, School of Medicine, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandAbstract Background High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC) with poor prognosis. In most cases EOC is widely disseminated at the time of diagnosis. Despite the optimal cytoreductive surgery and chemotherapy most patients develop chemoresistance, and the 5-year overall survival being only 25–35%. Methods Here we analyzed the gene expression profiles of 10 primary HGSOC tumors and 10 related omental metastases using RNA sequencing and identified 100 differentially expressed genes. Results The differentially expressed genes were associated with decreased embryogenesis and vasculogenesis and increased cellular proliferation and organismal death. Top upstream regulators responsible for this gene signature were NR5A1, GATA4, FOXL2, TP53 and BMP7. A subset of these genes were highly expressed in the ovarian cancer among the cancer transcriptomes of The Cancer Genome Atlas. Importantly, the metastatic gene signature was suggestive of poor survival in TCGA data based on gene enrichment analysis. Conclusion By comparing the gene expression profiles of primary HGSOC tumors and their matched metastasis, we provide evidence that a signature of 100 genes is able to separate these two sample types and potentially predict patient survival. Our study identifies functional categories of genes and transcription factors that could play important roles in promoting metastases and serve as markers for cancer prognosis.http://link.springer.com/article/10.1186/s12885-019-6339-0HGSOCOvarian carcinomaMetastasisRNA sequencingTranscriptome
spellingShingle H. Sallinen
S. Janhonen
P. Pölönen
H. Niskanen
O. H. Liu
A. Kivelä
J. M. Hartikainen
M. Anttila
M. Heinäniemi
S. Ylä-Herttuala
M. U. Kaikkonen
Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
BMC Cancer
HGSOC
Ovarian carcinoma
Metastasis
RNA sequencing
Transcriptome
title Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
title_full Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
title_fullStr Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
title_full_unstemmed Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
title_short Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
title_sort comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
topic HGSOC
Ovarian carcinoma
Metastasis
RNA sequencing
Transcriptome
url http://link.springer.com/article/10.1186/s12885-019-6339-0
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