EZH2/H3K27Me3 and phosphorylated EZH2 predict chemotherapy response and prognosis in ovarian cancer

PeerJ

article

Si Sun¹  Qiang Yang¹  E Cai¹  Bangxing Huang²  Feiquan Ying¹  Yiping Wen¹  Jing Cai¹  Ping Yang¹ 

[1] Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Obstetrics and Gynecology, First Affiliated Hospital, School of Medicine, Shihezi University

关键词: Ovarian cancer;    Prognosis;    Chemotherapy response;    Phosphorylated EZH2;    EZH2;    H3K27me3;    P-Akt1;    Overall survival;    Progression-free survival;    HGSOC;   

DOI  :  10.7717/peerj.9052

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundEZH2 acts as an oncogene through canonical pathway EZH2/H3K27Me3 and uncanonical pathway pAkt1/pS21EZH2 in many solid tumors including ovarian cancer. However, the clinical value of EZH2/H3K27Me3 and pAkt1/pS21EZH2 remain unclear. In the current study, we aim to investigate the correlation between these two pathways to clinical-pathological parameters and prognosis.MethodsEZH2, H3K27Me3, pAkt1 and pS21EZH2 expression were evaluated by tissue micro-array and immunohistochemistry in a cohort of ovarian cancer patients. The results were analyzed based on clinical characteristics and survival outcomes.ResultsEZH2, H3K27Me3, pAkt1 and pS21EZH2 were universally expressed in ovarian cancer specimens with a positive expression rate of 81.54% (53/65), 88.89% (48/54), 63.07% (41/65) and 75.38% (49/65). EZH2-pS21EZH2 (Spearman r = 0.580, P < 0.0001) and pS21EZH2-pAkt1 (Spearman r = 0.546, P < 0.0001) were closely correlated while EZH2- H3K27Me3 were less closely correlated (Spearman r = 0.307, P = 0.002). Low pS21EZH2 associated with better chemotherapy response (OR = 0.184; 95% CI [0.052–0.647], P = 0.008) according to logistic regression with an area under the curve of 0.789 (specificity 89.36%, sensitivity 68.42%) by ROC analysis and predicted improved progression-free survival (HR = 0.453; 95% CI [0.229–0.895], P = 0.023) as indicated by multivariate cox regression. A combination of EZH2low/H3K27Me3low status predicted better chemotherapy response (OR = 0.110; 95% CI [0.013–0.906], P = 0.040) and better progression-free survival (HR = 0.388; 95% CI [0.164–0.917], P = 0.031). The results suggested that EZH2/H3K27Me3 and pEZH2 predicted chemotherapy response and progression-free survival in ovarian cancer.

【 授权许可】

CC BY