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IGFBP-rP1在子宫内膜腺癌中的表达及其意义

发布时间:2018-05-14 12:51

  本文选题:子宫内膜肿瘤 + 胰岛素样生长因子结合蛋白相关蛋白1(IGFBP-rP1) ; 参考:《郑州大学》2014年硕士论文


【摘要】:背景与目的: 子宫内膜癌是女性生殖系统最常见的三大恶性肿瘤之一,近年来发病率逐渐上升,但治愈率未见明显改善。子宫内膜腺癌属I型子宫内膜癌,现普遍认为,以肥胖、高血压、高脂血症、糖尿病为特征的代谢综合症的人群为子宫内膜腺癌的高发人群,而代谢综合征发病的中心环节是胰岛素抵抗,因此,胰岛素抵抗与子宫内膜腺癌关系成为近年来该领域的研究热点。胰岛素样生长因子(IGF)系统是近年来研究胰岛素抵抗的焦点。胰岛素样生长因子结合蛋白(IGFBP)是IGF系统中重要的组成部分,目前共发现15个家族成员,根据与IGF结合能力的强弱,将其分为两类:IGFBPl-6与IGF具有较高的结合能力,而后续发现的IGFBP7-15与IGF的结合能力较低,因此又被称为胰岛素样生长因子结合蛋白相关蛋白(IGFBP-rP),IGFBP-rP1即IGFBP-7,因其与胰岛素的强结合能力而受到广泛关注。与IGFBP-rP1结合后的胰岛素失去或降低生理效应,,导致胰岛素敏感性下降,引起胰岛素抵抗,并参与某些恶性肿瘤如结肠癌、乳腺癌、胰腺癌等的发生发展。IGFBP-rP1在子宫内膜癌中的研究较少,本研究旨在探讨lGFBP-rPl在子宫内膜腺癌中的表达,并分析其表达情况与子宫内膜腺癌临床病理参数及与胰岛素抵抗之间的关系。 材料: 选取2011年1月-2012年12月郑州大学第一附属医院病理科存档的手术切除石蜡包埋子宫内膜病变组织标本共93例,其中子宫内膜样腺癌61例,子宫内膜非典型增生22例,子宫内膜简单性增生10例.术前均未接受放化疗及激素治疗。患者年龄36-72岁,中位年龄53岁。子宫内膜腺癌患者的平均身高为1.59m,平均体重为64.92kg,平均体重指数(BMI)25.83kg/m2,其中BMI≥25kg/m25O例,<25kg/m211例。FIGO(2000年)手术病理分期:Ⅰ期50例,Ⅱ期4例,Ⅲ期7例;病理分级:G1期29例,G2期29例,G3期3例;子宫肌层浸润深度:≤1/2者49例,>1/2者12例;术后证实有淋巴结转移者6例,无淋巴结转移者55例;合并高血压者49例,合并糖尿病者22例。 方法: 免疫组织化学法(SP法)检测三种子宫内膜组织中IGFBP-rP1蛋白表达情况,并分析IGFBP-rP1阳性表达率与子宫内膜腺癌临床病理参数之间的关系。应用实时荧光定量聚合酶链反应(RT-PCR)法检测石蜡组织中IGFBP-rP1mRNA的表达情况。 结果: 1.免疫组化法检测显示,子宫内膜样腺癌组织中的IGFBP-rP1阳性表达率(51/60,85.0%)显著高于子宫内膜非典型增生(14/22,63.6%)和子宫内膜简单性增生(2/10,20%)(χ2=16.764P<0.05);IGFBP-rP1的表达与子宫内膜癌的病理分级(χ2=3.399P<0.05)、超重(46/50,92.0%χ2=18.882P<0.01),合并高血压(44/49,89.8%,χ2=10.328P<0.01),糖尿病(21/22,95.5%χ2=4.235P<0.05)有关。与病理分期(χ2=4.783P0.05)、有无淋巴结转移(χ2=1.464P0.05)、浸润深度(χ2=0.019P0.05)无关. 2.RT-PCR检测结果显示,子宫内膜样腺癌中IGFBP-rP1mRNA表达量显著高于子宫内膜非典型增生组、简单性增生组(t=6.12,P<0.01t=4.45,P<0.01)。 结论: 1.IGFBP-rP1参与了子宫内膜腺癌的发生发展,并且可发挥促进子宫内膜癌细胞的增殖和去分化的作用; 2.IGFBP-rP1与胰岛素抵抗有关,IGFBP-rP1可能通过促进胰岛素抵抗来促进子宫内膜腺癌的发生;
[Abstract]:Background and purpose:
Endometrial carcinoma is one of the most common three malignant tumors in the female reproductive system. In recent years, the incidence of endometriosis is increasing, but the cure rate is not obviously improved. Endometrial adenocarcinoma is I type endometrial carcinoma. It is generally believed that the high level of endometrial adenocarcinoma with obesity, high blood pressure, hyperlipidemia and diabetes mellitus is the high level of endometrial adenocarcinoma. The central link of the metabolic syndrome is insulin resistance. Therefore, the relationship between insulin resistance and endometrial adenocarcinoma has become a hot topic in recent years. The insulin like growth factor (IGF) system is the focus of the study of insulin resistance in recent years. Insulin like growth factor binding protein (IGFBP) is an important part of the IGF system. A total of 15 family members have been found to be divided into two categories according to the strength of the IGF binding capacity. The combination of IGFBPl-6 and IGF has a higher binding capacity, and the subsequent discovery of the combination of IGFBP7-15 and IGF is lower, so it is also called the insulin like growth factor binding protein related protein (IGFBP-rP), IGFBP-rP1 is IGFBP-7, It is widely concerned because of its strong binding to insulin. The insulin loss or reduction of physiological effects after the combination of IGFBP-rP1 leads to a decline in insulin sensitivity and insulin resistance, and is involved in the development of some malignant tumors, such as colon, breast, and pancreatic cancer, and the development of.IGFBP-rP1 in endometrial cancer is less. The purpose of this study was to investigate the expression of lGFBP-rPl in endometrial adenocarcinoma, and to analyze the relationship between the expression of endometrial adenocarcinoma and the clinicopathological parameters of endometrial adenocarcinoma and the relationship with insulin resistance.
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