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H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival

Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied usi...

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Autores principales: Saravi, Sayeh, Katsuta, Eriko, Jeyaneethi, Jeyarooban, Amin, Hasnat A., Kaspar, Matthias, Takabe, Kazuaki, Pados, George, Drenos, Fotios, Hall, Marcia, Karteris, Emmanouil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565050/
https://www.ncbi.nlm.nih.gov/pubmed/32887437
http://dx.doi.org/10.3390/jcm9092844
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author Saravi, Sayeh
Katsuta, Eriko
Jeyaneethi, Jeyarooban
Amin, Hasnat A.
Kaspar, Matthias
Takabe, Kazuaki
Pados, George
Drenos, Fotios
Hall, Marcia
Karteris, Emmanouil
author_facet Saravi, Sayeh
Katsuta, Eriko
Jeyaneethi, Jeyarooban
Amin, Hasnat A.
Kaspar, Matthias
Takabe, Kazuaki
Pados, George
Drenos, Fotios
Hall, Marcia
Karteris, Emmanouil
author_sort Saravi, Sayeh
collection PubMed
description Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of H2AX expression to compare OS and perform gene set enrichment. qRT-PCR validated in-silico H2AX findings followed by immunohistochemistry on a tissue microarray. The association between single nucleotide polymorphisms in the area of H2AX; prevalence and five-year OC survival was tested in samples from the UK Biobank. Results: H2AX was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (p = 0.010). Gene Set Enrichment Analysis demonstrated gene sets involved in G2/M checkpoint, DNA repair mTORC1 signalling were enriched in the H2AX highly expressing OCs. Polymorphisms in the area around the gene were associated with both OC prevalence (rs72997349-C, p = 0.005) and worse OS (rs10790282-G, p = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. Conclusions: Our findings suggest that H2AX can be a novel prognostic biomarker for OC.
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spelling pubmed-75650502020-10-26 H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival Saravi, Sayeh Katsuta, Eriko Jeyaneethi, Jeyarooban Amin, Hasnat A. Kaspar, Matthias Takabe, Kazuaki Pados, George Drenos, Fotios Hall, Marcia Karteris, Emmanouil J Clin Med Article Background: H2AX can be of prognostic value in breast cancer, since in advanced stage patients with high levels, there was an association with worse overall survival (OS). However, the clinical relevance of H2AX in ovarian cancer (OC) remains to be elucidated. Methods: OC H2AX expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of H2AX expression to compare OS and perform gene set enrichment. qRT-PCR validated in-silico H2AX findings followed by immunohistochemistry on a tissue microarray. The association between single nucleotide polymorphisms in the area of H2AX; prevalence and five-year OC survival was tested in samples from the UK Biobank. Results: H2AX was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (p = 0.010). Gene Set Enrichment Analysis demonstrated gene sets involved in G2/M checkpoint, DNA repair mTORC1 signalling were enriched in the H2AX highly expressing OCs. Polymorphisms in the area around the gene were associated with both OC prevalence (rs72997349-C, p = 0.005) and worse OS (rs10790282-G, p = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. Conclusions: Our findings suggest that H2AX can be a novel prognostic biomarker for OC. MDPI 2020-09-02 /pmc/articles/PMC7565050/ /pubmed/32887437 http://dx.doi.org/10.3390/jcm9092844 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Saravi, Sayeh
Katsuta, Eriko
Jeyaneethi, Jeyarooban
Amin, Hasnat A.
Kaspar, Matthias
Takabe, Kazuaki
Pados, George
Drenos, Fotios
Hall, Marcia
Karteris, Emmanouil
H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title_full H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title_fullStr H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title_full_unstemmed H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title_short H2A Histone Family Member X (H2AX) Is Upregulated in Ovarian Cancer and Demonstrates Utility as a Prognostic Biomarker in Terms of Overall Survival
title_sort h2a histone family member x (h2ax) is upregulated in ovarian cancer and demonstrates utility as a prognostic biomarker in terms of overall survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565050/
https://www.ncbi.nlm.nih.gov/pubmed/32887437
http://dx.doi.org/10.3390/jcm9092844
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