Vattai Aurelia, Cavailles Vincent, Sixou Sophie, Beyer Susanne, Kuhn Christina, Peryanova Mina, Heidegger Helene, Hermelink Kerstin, Mayr Doris, Mahner Sven, Dannecker Christian, Jeschke Udo, Kost Bernd
Department of Gynaecology and Obstetrics, Ludwig-Maximilians University of Munich, 80337 Munich, Germany.
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université Montpellier, F-34298 Montpellier, France.
Oncotarget. 2017 Oct 31;8(62):105356-105371. doi: 10.18632/oncotarget.22187. eCollection 2017 Dec 1.
RIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival.
Immunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in formalin-fixed paraffin-embedded tissue sections cervical cancer samples. Correlations of RIP140 and LCoR expression with histopathological variables were determined by correlation analyses. Survival rates of patients expressing low or high levels of RIP140 and LCoR were compared by Kaplan-Meier curves.
RIP140 overexpression was associated with a significantly shorter overall survival of cervical cancer patients. This effect was significant in the squamous cell carcinoma subtype but not in adenocarcinomas. RIP140 is no longer a significant negative prognosticator for cervical cancer when LCoR expression is low.
RIP140 is an independent predictor of poor survival of patients with cervical cancer. Patients with tumors expressing low levels of both RIP140 and LCoR showed a better survival compared to patients expressing high levels of RIP140. Modulation of RIP140 and LCoR may represent a novel targeting strategy for cervical cancer prevention and therapy.
RIP140(受体相互作用蛋白)参与致癌信号通路的调控以及乳腺癌和结肠癌的发生发展。本研究旨在分析RIP140及其伴侣蛋白LCoR在宫颈癌中的表达情况,解读它们与组蛋白修饰的关系,并确定与患者生存的潜在联系。
采用免疫组织化学分析方法对福尔马林固定石蜡包埋的宫颈癌组织切片中RIP140和LCoR的表达进行定量。通过相关性分析确定RIP140和LCoR表达与组织病理学变量的相关性。采用Kaplan-Meier曲线比较RIP140和LCoR表达水平低或高的患者的生存率。
RIP140过表达与宫颈癌患者的总生存期显著缩短相关。这种效应在鳞状细胞癌亚型中显著,但在腺癌中不显著。当LCoR表达水平低时,RIP140不再是宫颈癌的显著负性预后指标。
RIP140是宫颈癌患者生存不良的独立预测指标。与RIP140表达水平高的患者相比,RIP140和LCoR表达水平均低的肿瘤患者生存率更高。调节RIP140和LCoR可能代表一种预防和治疗宫颈癌的新型靶向策略。