卵巢上皮性癌组织中GRIM-19蛋白的表达及其临床意义

摘要

Objective To investigate the expression and clinicopathological features of gene associated with retinoid-interferon mortality-19 (GRIM-19) in epithelial ovarian carcinoma.Methods The expression of GRIM-19 gene in tissues from 138 cases of epithelial ovarian carcinoma,102 cases of benign ovarian epithelial tumor and 46 cases of normal ovarian tissues were detected by Immunohistochemistry and Western blot methods.Assembled clinical survival data were analyzed with Kaplan-Meier and Cox regression models.Results The expression level of GRIM-19 in epithelial ovarian carcinoma (3.4 ± 2.0) was lower than that in benign ovarian tumor tissues (4.7 ± 2.9) and that in normal ovarian tissues (7.5 ± 2.2 ; P ＜0.01).The level of GRIM-19 expression was related to the survival time of epithelial ovarian carcinoma patients by Kaplan-Meier analysis (P =0.002).The shorter survival time of epithelial ovarian carcinoma patients was significantly associated with the level of GRIM-19 expression (P =0.001),clinical stage (P =0.001),volume of ascites (P =0.023) and the largest diameter of the primary tumor lesion (P =0.044) by Cox regression models.Conclusions The low expression of GRIM-19 in the epithelial ovarian carcinoma suggests that GRIM-19 may be a key gene involved in its carcinogenesis.The expression level of GRIM-19 may be also an independent prognostic factor for epithelial ovarian carcinoma patients.%目的 探讨细胞凋亡相关基因19(GRIM-19)蛋白在卵巢上皮性癌(卵巢癌)组织中的表达及其与卵巢癌患者临床病理指标和预后的关系.方法 收集2000年1月-2006年12月在浙江大学医学院附属妇产科医院手术切除的138份卵巢癌、101份卵巢良性上皮性肿瘤和46份正常卵巢组织标本,采用免疫组化法检测其GRIM-19蛋白的表达水平.并采用Mann-Whiteny U和Kruskal-Wallis H检验进行非参数分析,比较不同临床病理指标的卵巢癌组织中GRIM-19蛋白的表达水平；采用Kaplan-Meier和log-rank检验进行单因素生存分析,比较不同GRIM-19蛋白表达水平(分为阴性、弱阳性、中等阳性、强阳性组)的卵巢癌患者的预后；采用多因素Cox回归模型,分析影响卵巢癌患者预后的因素.结果 免疫组化法检测显示,卵巢癌、卵巢良性上皮性肿瘤、正常卵巢组织中GRIM-19蛋白的表达水平分别为(3.4±2.0)、(4.7±2.9)和(7.5±2.2)分,两两比较,差异均有统计学意义(P ＜0.01)；3 者间比较,差异也有统计学意义(P＜0.01).非参数分析显示,GRIM-19蛋白的表达水平与卵巢癌患者的腹水量明显相关(P =0.043),而与卵巢癌患者的年龄、血清CA125水平、病理分化程度、病理类型、手术病理分期、淋巴结转移、原发肿瘤最大直径、术后残留灶直径无关(P＞0.05).GRIM-19蛋白表达阴性、弱阳性、中等阳性、强阳性组卵巢癌患者分别为38、77、21、2例,单因素生存分析显示,4组间总生存时间比较,差异有统计学意义(P =0.002)；4组间无瘤生存时间比较,差异也有统计学意义(P=0.008).多因素Cox回归模型分析显示,GRIM-19蛋白表达水平(P=0.001)、手术病理分期(P =0.001)、腹水量(P=0.023)和原发肿瘤最大直径(P =0.044)是影响卵巢癌患者预后的独立因素.结论 GRIM-19蛋白在卵巢癌组织中的表达明显下降,提示GRIM-19可能是一种新的抑癌基因；GRIM-19蛋白的表达水平是影响卵巢癌患者预后的独立因素,提示其对卵巢癌患者的预后可能有预测价值.