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Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas

BACKGROUND: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian ca...

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Autores principales: Engqvist, Hanna, Parris, Toshima Z., Kovács, Anikó, Nemes, Szilárd, Werner Rönnerman, Elisabeth, De Lara, Shahin, Biermann, Jana, Sundfeldt, Karin, Karlsson, Per, Helou, Khalil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751742/
https://www.ncbi.nlm.nih.gov/pubmed/31533654
http://dx.doi.org/10.1186/s12885-019-6084-4
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author Engqvist, Hanna
Parris, Toshima Z.
Kovács, Anikó
Nemes, Szilárd
Werner Rönnerman, Elisabeth
De Lara, Shahin
Biermann, Jana
Sundfeldt, Karin
Karlsson, Per
Helou, Khalil
author_facet Engqvist, Hanna
Parris, Toshima Z.
Kovács, Anikó
Nemes, Szilárd
Werner Rönnerman, Elisabeth
De Lara, Shahin
Biermann, Jana
Sundfeldt, Karin
Karlsson, Per
Helou, Khalil
author_sort Engqvist, Hanna
collection PubMed
description BACKGROUND: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. METHODS: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC). RESULTS: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)). CONCLUSIONS: The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-6084-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-67517422019-09-23 Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas Engqvist, Hanna Parris, Toshima Z. Kovács, Anikó Nemes, Szilárd Werner Rönnerman, Elisabeth De Lara, Shahin Biermann, Jana Sundfeldt, Karin Karlsson, Per Helou, Khalil BMC Cancer Research Article BACKGROUND: Ovarian cancer is the main cause of gynecological cancer-associated death. However, 5-year survival rates differ dramatically between the five main ovarian carcinoma histotypes. Therefore, we need to have a better understanding of the mechanisms that promote histotype-specific ovarian carcinogenesis and identify novel prognostic biomarkers. METHODS: Here, we evaluated the prognostic role of 29 genes for early-stage (I and II) ovarian carcinomas (n = 206) using immunohistochemistry (IHC). RESULTS: We provide evidence of aberrant protein expression patterns for Collagen type III alpha 1 chain (COL3A1), G protein-coupled receptor 158 (GPR158) and PITH domain containing 1 (PITHD1). Kaplan-Meier survival analysis revealed that COL3A1 expression was associated with shorter overall survival in the four major histotypes of epithelial ovarian carcinoma patients (P value = 0.026, HR = 2.99 (95% CI 1.089–8.19)). Furthermore, GPR158 and PITHD1 were shown to be histotype-specific prognostic biomarkers, with elevated GPR158 expression patterns in mucinous ovarian carcinoma patients with unfavorable overall survival (P value = 0.00043, HR = 6.13 (95% CI 1.98–18.98)), and an association with lower PITHD1 protein expression and unfavorable overall and disease-specific survival in clear-cell ovarian carcinoma patients (P value = 0.012, HR = 0.22 (95% CI 0.058–0.80); P value = 0.003, HR = 0.17 (95% CI 0.043–0.64)). CONCLUSIONS: The novel biomarkers identified here may improve prognostication at the time of diagnosis and may assist in the development of future individualized therapeutic strategies for ovarian carcinoma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-6084-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-09-18 /pmc/articles/PMC6751742/ /pubmed/31533654 http://dx.doi.org/10.1186/s12885-019-6084-4 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
Engqvist, Hanna
Parris, Toshima Z.
Kovács, Anikó
Nemes, Szilárd
Werner Rönnerman, Elisabeth
De Lara, Shahin
Biermann, Jana
Sundfeldt, Karin
Karlsson, Per
Helou, Khalil
Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title_full Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title_fullStr Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title_full_unstemmed Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title_short Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas
title_sort immunohistochemical validation of col3a1, gpr158 and pithd1 as prognostic biomarkers in early-stage ovarian carcinomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751742/
https://www.ncbi.nlm.nih.gov/pubmed/31533654
http://dx.doi.org/10.1186/s12885-019-6084-4
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