Department of Gynecology and Obstetrics, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.
Laboratory of Gynecologic Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.
Aging (Albany NY). 2020 Nov 10;12(22):23029-23046. doi: 10.18632/aging.104049.
Two transcriptional factors, peroxisome proliferator-activated receptor-γ (PPARγ) and estrogen-related receptor-α (ERRα), have been reported to be key regulators of cellular energy metabolism. However, the relationship between ERRα and PPARγ in the development of endometrial cancer (EC) is still unclear. The expression levels of PPARγ and ERRα in EC were evaluated by quantitative real-time PCR, western blot, tissue array and immunohistochemistry. A significant negative correlation was identified between PPARγ and ERRα expression in women with EC (ρ=-0.509, P<0.001). Bioinformatics analyses showed that PPARγ and ERRα can activate or inhibit the same genes involved in cell proliferation and apoptosis through a similar ModFit. ERRα activation or PPARγ inhibition could promote proliferation and inhibit apoptosis through the Bcl-2/Caspase3 pathways. Both PPARγ and ERRα can serve as serum tumor markers. Surprisingly, as evaluated by receiver operating characteristic (ROC) curves and a logistic model, a PPARγ/ERRα ratio≤1.86 (area under the ROC curve (AUC)=0.915, Youden index=0.6633, P<0.001) was an independent risk factor for endometrial carcinogenesis (OR=14.847, 95% CI= 1.6-137.748, P=0.018). EC patients with PPARγ(-)/ERRα(+) had the worst overall survival and disease-free survival rates (both P<0.001). Thus, a dynamic imbalance between PPARγ and ERRα leads to endometrial carcinogenesis and predicts the EC prognosis.
两种转录因子，过氧化物酶体增殖物激活受体-γ（PPARγ）和雌激素相关受体-α（ERRα），已被报道为细胞能量代谢的关键调节因子。然而，ERRα与 PPARγ 在子宫内膜癌（EC）发展中的关系尚不清楚。通过定量实时 PCR、western blot、组织阵列和免疫组织化学评估了 PPARγ 和 ERRα 在 EC 中的表达水平。在患有 EC 的女性中，PPARγ 和 ERRα 的表达呈显著负相关（ρ=-0.509，P<0.001）。生物信息学分析表明，PPARγ 和 ERRα 可以通过相似的 ModFit 激活或抑制参与细胞增殖和凋亡的相同基因。ERRα 激活或 PPARγ 抑制可以通过 Bcl-2/Caspase3 途径促进增殖并抑制凋亡。PPARγ 和 ERRα 均可作为血清肿瘤标志物。令人惊讶的是，通过接收者操作特征（ROC）曲线和逻辑模型评估，PPARγ/ERRα 比值≤1.86（ROC 曲线下面积（AUC）=0.915，Youden 指数=0.6633，P<0.001）是子宫内膜癌发生的独立危险因素（OR=14.847，95%CI=1.6-137.748，P=0.018）。PPARγ（-）/ERRα（+）的 EC 患者总生存率和无病生存率最差（均 P<0.001）。因此，PPARγ 和 ERRα 之间的动态失衡导致子宫内膜癌发生，并预测 EC 预后。
