Prognostic role of GPER/Ezrin in triple-negative breast cancer is associated with menopausal status
Prognostic role of GPER/Ezrin in triple-negative breast cancer is associated with menopausal status
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GPER/Ezrin 在三阴性乳腺癌中的预后作用与绝经状态相关
DOI：
10.1530/ec-19-0164
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发表时间：
2019-06-01
影响因子：
2.9
通讯作者：
Wang, Tinghuai
中科院分区：
文献类型：
--
作者：
Ye, Shuang;Xu, Yuanyuan;Wang, Tinghuai
G蛋白偶联雌激素受体1(GPER)信号通路在三阴性乳腺癌(TNBC)中的作用尚不清楚，包括促进Ezrin磷酸化(可被雌激素激活)。本研究旨在评价GPER和Ezrin在TNBC患者中的预后价值。分析249例TNBC的临床病理特征，包括年龄、绝经状况、肿瘤大小、核分级、淋巴结转移、AJCC的TNM分期、ER、PR和HER-2的表达。对TNBC病理切片进行GPER和Ezrin免疫组织化学染色。采用Kaplan-Meier分析、Logistic回归和Cox回归模型检验来评价不同亚组间的预后意义。与GPER-Low组相比，GPER-HIGH组具有更高的TNM分期(P = 0.021)、更多的死亡(P <； 0.001)、复发(P <； 0.001)和远处事件(P <； 0.001)。Kaplan-Meier分析显示，与GPER低患者相比，高GPER患者的OS(P <； 0.001)、PFS(P <； 0.001)、LRF(P <； 0.001)和DDFS(P <； 0.001)降低。然而，绝经后患者的预后差异无统计学意义(OS，P = 0.8617；PFS，P = 0.1905；LRF，P = 0.4378；DDFS，P = 0.2538)。GPER与Ezrin表达水平呈显著正相关(R = 0.508，P <； 0.001)，且Ezrin对生存预后的影响与GPER一致。多因素分析表明，GPER和Ezrin水平均与DDFS相关(HR：0.346，95%CI 0.182~0.658，P = 0.001；HR：0.320，95%CI 0.162~0.631，P = 0.001)。因此，GPER和Ezrin的过度表达可能导致TNBC的攻击行为，并预示着不良的预后；这可能与个体的雌激素水平相对应。
The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.