STC-2在宮頸癌表達(dá)的功能研究及其臨床意義
發(fā)布時間:2018-04-21 14:40
本文選題:斯鈣素2 + 表達(dá) ; 參考:《南京醫(yī)科大學(xué)》2016年博士論文
【摘要】:研究背景:宮頸癌是女性最常見的生殖系統(tǒng)惡性腫瘤,其發(fā)病率和死亡率在全球女性惡性腫瘤中均位列第4。探索敏感、有效的宮頸癌生物標(biāo)記,以協(xié)助診斷、指導(dǎo)治療及預(yù)測療效,是腫瘤臨床診治的一項重點。斯鈣素-2(stanniocalcin 2, STC2)是一類糖蛋白激素,在人體組織中有廣泛表達(dá),參與調(diào)節(jié)多種生理、病理過程。近年的系列研究表明,STC2與多種腫瘤的發(fā)生、發(fā)展存在密切關(guān)聯(lián)。但是有關(guān)STC2與宮頸癌臨床病理因素的相關(guān)性,及能否預(yù)測宮頸癌的放療療效,目前尚無明確結(jié)論。本研究試圖通過樣本檢測、細(xì)胞株實驗和宮頸癌臨床病理參數(shù)分析及放療后生存期隨訪,驗證STC2在腫瘤組織的表達(dá)及其臨床意義,觀察STC2表達(dá)與宮頸癌細(xì)胞株增殖、遷移和侵襲的關(guān)聯(lián),并評估STC2在宮頸癌放療療效方面的預(yù)測價值。目的:評估STC2在宮頸癌的表達(dá)狀況,分析其表達(dá)對腫瘤細(xì)胞功能的影響,以及對于宮頸癌患者的臨床意義。方法:(1)收集50例宮頸癌腫瘤標(biāo)本,采用熒光定量PCR的方法檢測宮頸癌以及癌旁正常組織中STC2 mRNA的表達(dá)情況;采用western blot法檢測宮頸癌組織以及相應(yīng)癌旁正常組織中STC2蛋白的表達(dá)情況;分析宮頸癌組織中STC2的表達(dá)與宮頸癌患者臨床病理因素的相關(guān)性。(2)將si-STC2轉(zhuǎn)染宮頸癌Hela細(xì)胞株以沉默細(xì)胞中STC2的表達(dá)。對轉(zhuǎn)染后的Hela細(xì)胞株用western blot法檢測STC2蛋白的表達(dá)情況,并用CCK-8法檢測其增殖能力,用Transwe Ⅱ小室法檢測轉(zhuǎn)染后Hela細(xì)胞的侵襲性,用細(xì)胞劃痕實驗評估轉(zhuǎn)染si-STC2對Hela細(xì)胞遷移性的影響。(3)收集本院自2004~2007年期間診治的,共92例宮頸癌病理組織標(biāo)本,記錄臨床病理參數(shù),進(jìn)行放療后生存隨訪平均5年。檢測宮頸癌以及癌旁正常組織中STC2 mRNA及蛋白的表達(dá)情況;統(tǒng)計分析STC2表達(dá)與宮頸癌患者臨床病理參數(shù)之間的相關(guān)性;用Kaplan-Meier生存曲線,對STC2表達(dá)與放療后患者的總生存期(overall survival, OS)及無疾病進(jìn)展生存期(progress free survival, PFS)進(jìn)行相關(guān)分析;用Cox比例風(fēng)險回歸模型對獨(dú)立預(yù)后因子進(jìn)行多因素回歸分析。結(jié)果:(1)宮頸癌組織中的STC2 mRNA和蛋白表達(dá)顯著高于正常組織;STC2的表達(dá)與宮頸癌患者年齡、FIGO分期、腫瘤大小、病理分化程度、病理鱗癌/腺癌無明顯關(guān)聯(lián),而與淋巴結(jié)轉(zhuǎn)移有關(guān)(尸=0.0020.01)。(2)下調(diào)STC2基因后Hela細(xì)胞的增殖、侵襲以及遷移能力減弱。(3)STC2在宮頸癌腫瘤組織高表達(dá)患者放療后的OS(P=0.0130.05)和PFS(P=0.0040.01)均較低表達(dá)者短;另外淋巴結(jié)轉(zhuǎn)移患者的OS較短(P=0.0350.05)。結(jié)論:(1) STC2 mRNA和蛋白在宮頸癌組織的表達(dá)顯著高于正常組織;(2)STC2能夠促進(jìn)宮頸癌Hela細(xì)胞的增殖、侵襲和轉(zhuǎn)移;(3)STC2表達(dá)與宮頸癌患者的淋巴結(jié)轉(zhuǎn)移相關(guān);(4)STC2表達(dá)與宮頸癌患者的OS和PFS呈顯著負(fù)相關(guān)。
[Abstract]:Background: cervical cancer is the most common malignant tumor of the reproductive system in women. To explore sensitive and effective biomarkers for diagnosis, treatment and prognosis of cervical cancer is an important point in clinical diagnosis and treatment of cancer. Statin-2 stanniocalcin 2 (STC2) is a kind of glycoprotein hormone, which is widely expressed in human tissues and participates in many physiological and pathological processes. A series of studies in recent years have shown that STC2 is closely related to the occurrence and development of many kinds of tumors. However, there is no clear conclusion about the correlation between STC2 and clinicopathological factors of cervical cancer, and whether it can predict the curative effect of radiotherapy for cervical cancer. The purpose of this study was to verify the expression of STC2 in tumor tissue and its clinical significance, and to observe the expression of STC2 and the proliferation of cervical cancer cell line by means of sample detection, cell line test, clinicopathologic parameters analysis and survival follow-up after radiotherapy. Relationship between migration and invasion, and evaluation of STC2 in predicting the efficacy of radiotherapy for cervical cancer. Aim: to evaluate the expression of STC2 in cervical cancer, and to analyze its effect on tumor cell function and its clinical significance. Methods 50 specimens of cervical carcinoma were collected. The expression of STC2 mRNA in cervical carcinoma and adjacent normal tissues was detected by fluorescence quantitative PCR. Western blot method was used to detect the expression of STC2 protein in cervical carcinoma tissues and adjacent normal tissues. To analyze the correlation between the expression of STC2 and the clinicopathological factors of cervical carcinoma. (2) transfection of si-STC2 into cervical cancer Hela cell line to silence the expression of STC2 in cervical cancer cells. After transfection, the expression of STC2 protein was detected by western blot assay, the proliferative ability was detected by CCK-8 assay, and the invasiveness of Hela cells after transfection was detected by Transwe 鈪,
本文編號:1782859
本文鏈接:http://sikaile.net/yixuelunwen/zlx/1782859.html
最近更新
教材專著