EZH2/H3K27Me3 and phosphorylated EZH2 predict chemotherapy response and prognosis in ovarian cancer
EZH2/H3K27Me3 and phosphorylated EZH2 predict chemotherapy response and prognosis in ovarian cancer
复制标题
EZH2/H3K27Me3 和磷酸化 EZH2 预测卵巢癌的化疗反应和预后
DOI：
10.7717/peerj.9052
复制
发表时间：
2020-05-12
期刊：
影响因子：
2.7
通讯作者：
Yang, Ping
中科院分区：
文献类型：
--
作者：
Sun, Si;Yang, Qiang;Yang, Ping
背景EZH 2作为一种癌基因，通过经典途径EZH 2/H3 K27 Me 3和非经典途径pAkt 1/pS21 EZH 2在包括卵巢癌在内的许多实体瘤中发挥作用。然而，EZH 2/H3 K27 Me 3和pAkt 1/pS21 EZH 2的临床价值尚不清楚。在目前的研究中，我们的目的是调查这两个途径之间的相关性，临床病理参数和预后。方法应用组织芯片和免疫组化技术检测EZH 2、H3 K27 Me 3、pAkt 1和pS21 EZH 2在卵巢癌患者中的表达。根据临床特征和生存结局对结果进行分析。结果EZH 2、H3 K27 Me 3、pAkt 1和pS21 EZH 2在卵巢癌组织中普遍表达，阳性表达率分别为81.54%（53/65）、88.89%（48/54）、63.07%（41/65）和75.38%（49/65）。EZH 2-pS21 EZH 2（斯皮尔曼r = 0.580，P < 0.0001）和pS21 EZH 2-pAkt 1（斯皮尔曼r = 0.546，P < 0.0001）密切相关，而EZH 2-H3 K27 Me 3不太密切相关（斯皮尔曼r = 0.307，P = 0.002）。低pS21 EZH 2与更好的化疗反应相关根据Logistic回归，OR = 0.184; 95%CI [0.052-0.647]，P = 0.008，曲线下面积为0.789 ROC曲线分析显示，特异性为89.36%，敏感性为68.42%，预测无进展生存期的改善（HR = 0.453; 95% CI [0.229-0.895]，P = 0.023）。EZH 2low/H3 K27 Me 3low状态的组合预测更好的化疗反应（OR = 0.110; 95%CI [0.013-0.906]，P = 0.040）和更好的无进展生存期（HR = 0.388; 95%CI [0.164-0.917]，P = 0.031）。结果表明，EZH 2/H3 K27 Me 3和pEZH 2预测卵巢癌的化疗反应和无进展生存。
Background EZH2 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. Methods EZH2, 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. Results EZH2, 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.