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

Abstract

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.

A pancancer overview of FBN1, asprosin and its cognate receptor OR4M1 with detailed expression profiling in ovarian cancer

“…Immunoreactivity was analysed using a light microscope (Zeiss GmbH). Results were calculated by two independent reviewers using a percentage score of positive tumour cells, as described previously ( 24 ).…”

“…Additional primers include the housekeeping gene YWHAZ ( Table IV ). RQ values were calculated as previously described ( 24 ), according to the comparative 2 −ΔΔCq analysis method ( 25 ).…”

Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer

“…Histone H2AX, one of the first known substrates for ATR and ATM kinases, is expressed in high-grade SOC, mucinous adenocarcinomas, and clear cell carcinomas. Significant changes in the gene and protein levels of H2AX have been reported in OC, supporting its predictive value as a biomarker [ 96 ].…”

Roles of Histone H2A Variants in Cancer Development, Prognosis, and Treatment

“…Surprisingly, H2A.X is found selectively overexpressed in normal adjacent tissue (NAT) rather than its origin of malignancy in OC. Extracellular matrix remodeling and epithelial-to-mesenchymal transition (EMT) are observed in these NAT, suggesting that H2A.X may exert a role in helping NAT to obtain well-prepared via cross-talking with cancer microenvironment ( Figure 2 A) [ 52 ]. However, the underlying principles of how a high level of H2A.X in NAT can lead to EMT stays unclear.…”