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

• Main Authors: Sayeh Saravi, Eriko Katsuta, Jeyarooban Jeyaneethi, Hasnat A. Amin, Matthias Kaspar, Kazuaki Takabe, George Pados, Fotios Drenos, Marcia Hall, Emmanouil Karteris
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Journal of Clinical Medicine
• Subjects: H2AX; ovarian cancer; biomarker; polymorphisms
• Online Access: https://www.mdpi.com/2077-0383/9/9/2844

<i>Background</i>: 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. <i>Methods</i>: OC <i>H2AX </i>expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of <i>H2AX</i> expression to compare OS and perform gene set enrichment. qRT-PCR validated <i>in-silico H2AX</i> 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. <i>Results</i>: <i>H2AX</i> was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS (<i>p </i>= 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, <i>p </i>= 0.005) and worse OS (rs10790282-G, <i>p</i> = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. <i>Conclusions</i>: Our findings suggest that H2AX can be a novel prognostic biomarker for OC.