Tang Wenbo, Liu Rujiao, Yan Yan, Pan Xiaoli, Wang Minjun, Han Xiaotian, Ren Hui, Zhang Zhe
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China.
Oncotarget. 2017 Jun 20;8(25):40765-40777. doi: 10.18632/oncotarget.16582.
Despite the mounting studies exploring the role of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ) and androgen receptor (AR) in gastric cancer (GC), there remain controversies in those findings. The present study investigated the expression of ERα, ERβ and AR in Chinese gastric cancer by immunohistochemistry, analyzed their clinical relevance in gastric cancer, and examined the potential mechanisms by which ERα and AR modulated GC progression. The positive rate of ERα, ERβ and AR in GC tissues was 6% (9/150), 93.5% (143/153), and 42.4% (59/139), respectively. The expression of ERα was an independent unfavorable risk factor for overall survival (OS) (hazard ratio [HR] = 3.639, 95% confidence interval [CI] = 1.432-9.246, p = 0.007) for GC patients. Moreover, AR was borderline significantly associated with poor progress free survival (PFS) after adjustment with other variables (HR = 1.573, 95% CI = 0.955-2.592, p = 0.075). Knockdown of ERα inhibited the proliferation, migration and invasion of GC cells possibly via modulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. Downregulation of AR suppressed the migration and invasion of GC cells and inhibited the epithelial-mesenchymal transition (EMT) associated pathways.
The present study showed that positive ERα was associated with poor prognosis of Chinese GC patients. ERα might modulate the proliferation, migration and invasion via regulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. ERα could be a valuable prognostic biomarker and promising therapeutic target for Chinese GC patients.
尽管越来越多的研究探讨雌激素受体α(ERα)、雌激素受体β(ERβ)和雄激素受体(AR)在胃癌(GC)中的作用,但这些研究结果仍存在争议。本研究通过免疫组织化学研究了ERα、ERβ和AR在中国胃癌中的表达,分析了它们在胃癌中的临床相关性,并探讨了ERα和AR调节GC进展的潜在机制。GC组织中ERα、ERβ和AR的阳性率分别为6%(9/150)、93.5%(143/153)和42.4%(59/139)。ERα的表达是GC患者总生存期(OS)的独立不良危险因素(风险比[HR]=3.639,95%置信区间[CI]=1.432-9.246,p=0.007)。此外,在调整其他变量后,AR与无进展生存期(PFS)较差存在临界显著相关性(HR=1.573,95%CI=0.955-2.592,p=0.075)。敲低ERα可能通过调节p53、p21、p27、细胞周期蛋白D1和E-钙黏蛋白的表达来抑制GC细胞的增殖、迁移和侵袭。AR的下调抑制了GC细胞的迁移和侵袭,并抑制了上皮-间质转化(EMT)相关途径。
本研究表明,ERα阳性与中国GC患者的不良预后相关。ERα可能通过调节p53、p21、p27、细胞周期蛋白D1和E-钙黏蛋白的表达来调节增殖、迁移和侵袭。ERα可能是中国GC患者有价值的预后生物标志物和有前景的治疗靶点。