Saravi Sayeh, Katsuta Eriko, Jeyaneethi Jeyarooban, Amin Hasnat A, Kaspar Matthias, Takabe Kazuaki, Pados George, Drenos Fotios, Hall Marcia, Karteris Emmanouil
Department of Life Sciences, Brunel University London, Uxbridge UB83PH, UK.
Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
J Clin Med. 2020 Sep 2;9(9):2844. doi: 10.3390/jcm9092844.
: 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. : OC expression studied using the TCGA/GTEX datasets. Subsequently, patients were classified as either high or low in terms of expression to compare OS and perform gene set enrichment. qRT-PCR validated 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. : was significantly overexpressed in OCs compared to normal tissues, with higher expression associated with better OS ( = 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, = 0.005) and worse OS (rs10790282-G, = 0.011). Finally, we demonstrated that H2AX gene expression correlated with γ-H2AX staining in vitro. : Our findings suggest that H2AX can be a novel prognostic biomarker for OC.
H2AX在乳腺癌中可能具有预后价值,因为在晚期且H2AX水平高的患者中,其与较差的总生存期(OS)相关。然而,H2AX在卵巢癌(OC)中的临床相关性仍有待阐明。使用TCGA/GTEX数据集研究OC中的H2AX表达。随后,根据H2AX表达将患者分为高表达组或低表达组,以比较OS并进行基因集富集分析。qRT-PCR验证结果,随后在组织芯片上进行免疫组化。在英国生物银行的样本中测试H2AX区域单核苷酸多态性与OC患病率及五年生存率之间的关联。与正常组织相比,H2AX在OC中显著过表达,较高的表达与较好的OS相关(P = 0.010)。基因集富集分析表明,参与G2/M检查点、DNA修复和mTORC1信号传导的基因集在H2AX高表达的OC中富集。该基因周围区域的多态性与OC患病率(rs72997349 - C,P = 0.005)和较差的OS(rs10790282 - G,P = 0.011)均相关。最后,我们证明H2AX基因表达与体外γ - H2AX染色相关。我们的研究结果表明,H2AX可能是OC的一种新型预后生物标志物。