Enhancer of zeste homolog 2 (EZH2), a chromatin remodeler, is implicated in the pathogenesis of clear cell renal cell carcinoma (ccRCC). However, the effect of EZH2 on outcomes in localized ccRCC is unclear, and molecular biomarkers are not currently integrated into prognostic models or adjuvant therapy trials.

We performed Cox regression to evaluate the association of tumor-based EZH2 gene and protein expression with survival in three independent cohorts: a cohort from The Cancer Genome Atlas (n = 532), a cohort from University of Texas Southwestern Medical Center (n = 122), and a cohort from Mayo Clinic (n = 1,338). Analyses were adjusted for the prognostic stage, size, grade, and necrosis (SSIGN) score as well as within low-, intermediate-, and high-risk SSIGN groups.

Patients in The Cancer Genome Atlas cohort with EZH2-high gene expression were 1.5 times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 2.3; P = .028). Patients in the University of Texas Southwestern Medical Center cohort with EZH2-high protein expression were two times more likely to experience overall death than patients with EZH2-low expression (95% CI, 1.1 to 4.4; P = .034). Similarly, patients in the Mayo Clinic cohort with EZH2-high protein expression were 1.4 times more likely to experience overall death (95% CI, 1.2 to 1.7; P < .001). Patients in the Mayo Clinic cohort with EZH2-high protein expression were nearly two times more likely to experience RCC-specific death (95% CI, 1.5 to 2.6; P < .001); EZH2 protein expression was particularly prognostic among patients with low-risk SSIGN tumors (HR, 6.1; 95% CI, 3.4 to 11.1; P < .001).

EZH2 expression accurately predicts risk of RCC death beyond existing clinicopathologic models, particularly in low- and intermediate-risk SSIGN tumors. Further studies are required to incorporate molecular biomarkers into surveillance guidelines and adjuvant clinical trials.

zeste同源物2（EZH2）的增强子，一种染色质重塑剂，与透明细胞肾细胞癌（ccRCC）的发病机制有关。但是，EZH2对局部ccRCC结局的影响尚不清楚，并且分子生物标志物目前尚未整合到预后模型或辅助治疗试验中。

我们进行了Cox回归，以评估三个独立队列中基于肿瘤的EZH2基因和蛋白质表达与存活的关系：癌症基因组图谱（n = 532），德克萨斯大学西南医学中心（n = 122）队列），以及来自梅奥诊所的一组研究（n = 1,338）。对预后阶段，大小，等级和坏死（SSIGN）评分以及低，中和高风险SSIGN组的分析进行了调整。

在癌症基因组图谱的队列与患者EZH2 -高基因表达分别为1.5倍更有可能经历比患者总体死亡EZH2 -低表达（95％CI，1.1〜2.3; P = 0.028）。德克萨斯大学西南医学中心大学中EZH2蛋白高表达的患者发生整体死亡的可能性是EZH2蛋白低表达的患者整体死亡的可能性高两倍（95％CI，1.1到4.4；P = .034）。同样，梅奥诊所队列中具有EZH2高蛋白表达的患者发生整体死亡的可能性高1.4倍（95％CI，1.2至1.7；P<.001）。梅奥诊所队列中EZH2蛋白高表达的患者发生RCC特异性死亡的可能性高近两倍（95％CI，1.5至2.6；P <0.001）；EZH2蛋白表达在低危SSIGN肿瘤患者中尤其预后（HR，6.1； 95％CI，3.4至11.1；P <.001）。

EZH2表达可准确预测RCC死亡的风险，超越现有的临床病理模型，尤其是在中低危SSIGN肿瘤中。需要进一步的研究，以将分子生物标记物纳入监测指南和辅助临床试验。