Sun Si, Yang Qiang, Cai E, Huang Bangxing, Ying Feiquan, Wen Yiping, Cai Jing, Yang Ping
Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PeerJ. 2020 May 12;8:e9052. doi: 10.7717/peerj.9052. eCollection 2020.
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.
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.
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 = 0.580, < 0.0001) and pS21EZH2-pAkt1 (Spearman = 0.546, < 0.0001) were closely correlated while EZH2- H3K27Me3 were less closely correlated (Spearman = 0.307, = 0.002). Low pS21EZH2 associated with better chemotherapy response (OR = 0.184; 95% CI [0.052-0.647], = 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], = 0.023) as indicated by multivariate cox regression. A combination of EZH2/H3K27Me3 status predicted better chemotherapy response (OR = 0.110; 95% CI [0.013-0.906], = 0.040) and better progression-free survival (HR = 0.388; 95% CI [0.164-0.917], = 0.031). The results suggested that EZH2/H3K27Me3 and pEZH2 predicted chemotherapy response and progression-free survival in ovarian cancer.
在包括卵巢癌在内的许多实体瘤中，EZH2通过经典途径EZH2/H3K27Me3和非经典途径pAkt1/pS21EZH2发挥致癌基因的作用。然而，EZH2/H3K27Me3和pAkt1/pS21EZH2的临床价值仍不清楚。在本研究中，我们旨在探讨这两条途径与临床病理参数及预后之间的相关性。
通过组织芯片和免疫组化对一组卵巢癌患者评估EZH2、H3K27Me3、pAkt1和pS21EZH2的表达。根据临床特征和生存结果对结果进行分析。
EZH2、H3K27Me3、pAkt1和pS21EZH2在卵巢癌标本中均有普遍表达，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）。EZH2-pS21EZH2（Spearman=0.580，<0.0001）和pS21EZH2-pAkt1（Spearman=0.546，<0.0001）密切相关，而EZH2-H3K27Me3相关性较弱（Spearman=0.307，=0.002）。根据逻辑回归分析，低pS21EZH2与更好的化疗反应相关（OR=0.184；95%CI[0.052-0.647]，=0.008），ROC分析曲线下面积为0.789（特异性89.36%，敏感性68.42%），多因素cox回归分析表明其预测无进展生存期改善（HR=0.453；95%CI[0.229-0.895]，=0.023）。EZH2/H3K27Me3状态联合预测更好的化疗反应（OR=0.110；95%CI[0.013-0.906]，=0.040）和更好的无进展生存期（HR=0.388；95%CI[0.164-0.917]，=0.031）。结果表明，EZH2/H3K27Me3和pEZH2可预测卵巢癌的化疗反应和无进展生存期。
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