SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients’ outcome. Optimal thresholds for high and low expression of both variables were calculated by the Youden’s index based on receiver operating characteristic (ROC) curves. High SMARCA4 mRNA expression was independently associated with favorable progression-free survival (PFS) (P = 0.03) and overall survival (OS) (P = 0.018). As Youden’s threshold determination for EZH2 yielded a S-shaped ROC-curve, two cut-off points (29th and 94th percentile) predicting opposite features were defined. Whereas EZH2 mRNA levels beyond the 29th percentile independently predicted poor PFS (P = 0.034), Cox-regression in EZH2 transcripts above the 94th percentile revealed a conversion from unfavorable to favorable PFS and OS (P = 0.009 and P = 0.032, respectively). High SMARCA4 expression associates with improved survival, whereas moderate/high EZH2 expression predicts poor outcome, which converts to favorable survival in ultra-high expressing OCs. This small OC subgroup could be characterized by REV7-abrogated platinum hypersensitivity but concomitant PARP-inhibitor resistance.

SMARCA4和EZH2是它们各自拮抗的染色质重塑复合物SWI / SNF和PRC2的两个功能关键参与者。EZH2抑制药物可能会消除PRC2的促癌特性，并通过SWI / SNF活性将平衡转变为细胞分化。通过RT-PCR评估了238例上皮性卵巢癌（OCs）中SMARCA4和EZH2的表达，并将其与临床病理参数和患者预后相关。根据接收器工作特性（ROC）曲线，由Youden指数计算出两个变量的高低表达的最佳阈值。SMARCA4 mRNA高表达与良好的无进展生存期（PFS）独立相关（P = 0.03）和总生存期（OS）（P  = 0.018）。由于Youden对EZH2的阈值确定产生了S形ROC曲线，因此定义了两个预测相反特征的临界点（第29和94个百分位数）。而EZH2 mRNA水平超出了第29百分位独立预测差PFS（P  = 0.034），COX-回归在EZH2转录第94百分位数以上揭示从不利有利PFS和OS（转换P  = 0.009和P 分别= 0.032，）。SMARCA4高表达与存活率提高相关，而中/高EZH2表达预测不良结果，这将转化为超高表达OC的良好存活。这个小的OC亚组的特征可能是REV7废除的铂超敏反应，但同时伴有PARP抑制剂的耐药性。