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Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma

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 chemoresista...

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Autores principales: Sallinen, H., Janhonen, S., Pölönen, P., Niskanen, H., Liu, O. H., Kivelä, A., Hartikainen, J. M., Anttila, M., Heinäniemi, M., Ylä-Herttuala, S., Kaikkonen, M. U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862850/
https://www.ncbi.nlm.nih.gov/pubmed/31744494
http://dx.doi.org/10.1186/s12885-019-6339-0
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author Sallinen, H.
Janhonen, S.
Pölönen, P.
Niskanen, H.
Liu, O. H.
Kivelä, A.
Hartikainen, J. M.
Anttila, M.
Heinäniemi, M.
Ylä-Herttuala, S.
Kaikkonen, M. U.
author_facet Sallinen, H.
Janhonen, S.
Pölönen, P.
Niskanen, H.
Liu, O. H.
Kivelä, A.
Hartikainen, J. M.
Anttila, M.
Heinäniemi, M.
Ylä-Herttuala, S.
Kaikkonen, M. U.
author_sort Sallinen, H.
collection PubMed
description 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 pubmed-68628502019-12-11 Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma Sallinen, H. Janhonen, S. Pölönen, P. Niskanen, H. Liu, O. H. Kivelä, A. Hartikainen, J. M. Anttila, M. Heinäniemi, M. Ylä-Herttuala, S. Kaikkonen, M. U. BMC Cancer Research Article 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. BioMed Central 2019-11-19 /pmc/articles/PMC6862850/ /pubmed/31744494 http://dx.doi.org/10.1186/s12885-019-6339-0 Text en © The Author(s). 2019 Open AccessThis 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.
spellingShingle Research Article
Sallinen, H.
Janhonen, S.
Pölönen, P.
Niskanen, H.
Liu, O. H.
Kivelä, A.
Hartikainen, J. M.
Anttila, M.
Heinäniemi, M.
Ylä-Herttuala, S.
Kaikkonen, M. U.
Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862850/
https://www.ncbi.nlm.nih.gov/pubmed/31744494
http://dx.doi.org/10.1186/s12885-019-6339-0
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