IGFBP-rP1在子宮內(nèi)膜腺癌中的表達(dá)及其意義
發(fā)布時(shí)間:2018-05-14 12:51
本文選題:子宮內(nèi)膜腫瘤 + 胰島素樣生長因子結(jié)合蛋白相關(guān)蛋白1(IGFBP-rP1) ; 參考:《鄭州大學(xué)》2014年碩士論文
【摘要】:背景與目的: 子宮內(nèi)膜癌是女性生殖系統(tǒng)最常見的三大惡性腫瘤之一,近年來發(fā)病率逐漸上升,但治愈率未見明顯改善。子宮內(nèi)膜腺癌屬I型子宮內(nèi)膜癌,現(xiàn)普遍認(rèn)為,以肥胖、高血壓、高脂血癥、糖尿病為特征的代謝綜合癥的人群為子宮內(nèi)膜腺癌的高發(fā)人群,而代謝綜合征發(fā)病的中心環(huán)節(jié)是胰島素抵抗,因此,胰島素抵抗與子宮內(nèi)膜腺癌關(guān)系成為近年來該領(lǐng)域的研究熱點(diǎn)。胰島素樣生長因子(IGF)系統(tǒng)是近年來研究胰島素抵抗的焦點(diǎn)。胰島素樣生長因子結(jié)合蛋白(IGFBP)是IGF系統(tǒng)中重要的組成部分,目前共發(fā)現(xiàn)15個(gè)家族成員,根據(jù)與IGF結(jié)合能力的強(qiáng)弱,將其分為兩類:IGFBPl-6與IGF具有較高的結(jié)合能力,而后續(xù)發(fā)現(xiàn)的IGFBP7-15與IGF的結(jié)合能力較低,因此又被稱為胰島素樣生長因子結(jié)合蛋白相關(guān)蛋白(IGFBP-rP),IGFBP-rP1即IGFBP-7,因其與胰島素的強(qiáng)結(jié)合能力而受到廣泛關(guān)注。與IGFBP-rP1結(jié)合后的胰島素失去或降低生理效應(yīng),,導(dǎo)致胰島素敏感性下降,引起胰島素抵抗,并參與某些惡性腫瘤如結(jié)腸癌、乳腺癌、胰腺癌等的發(fā)生發(fā)展。IGFBP-rP1在子宮內(nèi)膜癌中的研究較少,本研究旨在探討lGFBP-rPl在子宮內(nèi)膜腺癌中的表達(dá),并分析其表達(dá)情況與子宮內(nèi)膜腺癌臨床病理參數(shù)及與胰島素抵抗之間的關(guān)系。 材料: 選取2011年1月-2012年12月鄭州大學(xué)第一附屬醫(yī)院病理科存檔的手術(shù)切除石蠟包埋子宮內(nèi)膜病變組織標(biāo)本共93例,其中子宮內(nèi)膜樣腺癌61例,子宮內(nèi)膜非典型增生22例,子宮內(nèi)膜簡單性增生10例.術(shù)前均未接受放化療及激素治療;颊吣挲g36-72歲,中位年齡53歲。子宮內(nèi)膜腺癌患者的平均身高為1.59m,平均體重為64.92kg,平均體重指數(shù)(BMI)25.83kg/m2,其中BMI≥25kg/m25O例,<25kg/m211例。FIGO(2000年)手術(shù)病理分期:Ⅰ期50例,Ⅱ期4例,Ⅲ期7例;病理分級:G1期29例,G2期29例,G3期3例;子宮肌層浸潤深度:≤1/2者49例,>1/2者12例;術(shù)后證實(shí)有淋巴結(jié)轉(zhuǎn)移者6例,無淋巴結(jié)轉(zhuǎn)移者55例;合并高血壓者49例,合并糖尿病者22例。 方法: 免疫組織化學(xué)法(SP法)檢測三種子宮內(nèi)膜組織中IGFBP-rP1蛋白表達(dá)情況,并分析IGFBP-rP1陽性表達(dá)率與子宮內(nèi)膜腺癌臨床病理參數(shù)之間的關(guān)系。應(yīng)用實(shí)時(shí)熒光定量聚合酶鏈反應(yīng)(RT-PCR)法檢測石蠟組織中IGFBP-rP1mRNA的表達(dá)情況。 結(jié)果: 1.免疫組化法檢測顯示,子宮內(nèi)膜樣腺癌組織中的IGFBP-rP1陽性表達(dá)率(51/60,85.0%)顯著高于子宮內(nèi)膜非典型增生(14/22,63.6%)和子宮內(nèi)膜簡單性增生(2/10,20%)(χ2=16.764P<0.05);IGFBP-rP1的表達(dá)與子宮內(nèi)膜癌的病理分級(χ2=3.399P<0.05)、超重(46/50,92.0%χ2=18.882P<0.01),合并高血壓(44/49,89.8%,χ2=10.328P<0.01),糖尿。21/22,95.5%χ2=4.235P<0.05)有關(guān)。與病理分期(χ2=4.783P0.05)、有無淋巴結(jié)轉(zhuǎn)移(χ2=1.464P0.05)、浸潤深度(χ2=0.019P0.05)無關(guān). 2.RT-PCR檢測結(jié)果顯示,子宮內(nèi)膜樣腺癌中IGFBP-rP1mRNA表達(dá)量顯著高于子宮內(nèi)膜非典型增生組、簡單性增生組(t=6.12,P<0.01t=4.45,P<0.01)。 結(jié)論: 1.IGFBP-rP1參與了子宮內(nèi)膜腺癌的發(fā)生發(fā)展,并且可發(fā)揮促進(jìn)子宮內(nèi)膜癌細(xì)胞的增殖和去分化的作用; 2.IGFBP-rP1與胰島素抵抗有關(guān),IGFBP-rP1可能通過促進(jìn)胰島素抵抗來促進(jìn)子宮內(nèi)膜腺癌的發(fā)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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