本文選題：上皮性卵巢癌　切入點(diǎn)：MTDH　出處：《鄭州大學(xué)》2014年碩士論文

【摘要】：上皮性卵巢癌是婦科常見的惡性腫瘤之一，其生存率近年來雖然已有所提高，但大多數(shù)確診時已為晚期，5年總體生存率仍未超過40％。腫瘤的發(fā)生發(fā)展與腫瘤新生血管的形成有密切關(guān)系，這些新生血管在卵巢腫瘤的生長、轉(zhuǎn)移和擴(kuò)散過程中均發(fā)揮重大作用。血管內(nèi)皮生長因子（vascular endothelial growthfactor，VEGF）不僅能使腫瘤血管的通透性增加，腫瘤細(xì)胞浸潤能力增強(qiáng)，而且能促進(jìn)血管內(nèi)皮細(xì)胞的增生，誘導(dǎo)腫瘤新生血管的形成，從而促進(jìn)腫瘤的發(fā)展和侵襲轉(zhuǎn)移。 異黏蛋白（Metadherin，MTDH）基因又名星形膠質(zhì)細(xì)胞升高基因1（astrocyteelevated gene1，AEG-1），是由人類免疫缺陷病毒1型（humanimmunodeficiency virus-1，HIV-1）感染人類胚胎性星形膠質(zhì)細(xì)胞或由腫瘤壞死因子-ɑ誘導(dǎo)產(chǎn)生的，其表達(dá)產(chǎn)物為MTDH。有研究表明MTDH既是一種致癌基因，又是血管形成的誘導(dǎo)因子，，其在乳腺癌、多形性膠質(zhì)母細(xì)胞瘤、惡性黑色素瘤、腎細(xì)胞癌、子宮內(nèi)膜癌、結(jié)直腸癌及胸腺癌等多種惡性腫瘤的發(fā)生、發(fā)展及瘤細(xì)胞轉(zhuǎn)移中發(fā)揮重大作用。有關(guān)其在上皮性卵巢癌中的研究甚少，其結(jié)果也不盡相同，需更進(jìn)一步研究。本研究通過RT-PCR及免疫組織化學(xué)SP法檢測不同卵巢上皮組織中MTDH mRNA、VEGF mRNA及兩者對應(yīng)蛋白的表達(dá)，探討其在卵巢上皮性腫瘤中的作用及應(yīng)用價值。 目的 探討MTDH、VEGF在上皮性卵巢癌中的表達(dá)及兩者與上皮性卵巢癌發(fā)生發(fā)展的關(guān)系；分析上皮性卵巢癌中MTDH蛋白及VEGF蛋白表達(dá)之間的相關(guān)性。 材料與方法 1.研究對象 收集鄭州大學(xué)第三附屬醫(yī)院婦產(chǎn)科2010年7月到2013年4月住院行手術(shù)切除的原發(fā)性上皮性卵巢癌組織（惡性組）42例，其中漿液性囊性癌25例、粘液性囊性癌10例、子宮內(nèi)膜樣癌7例；卵巢良性上皮性腫瘤組織（良性組）20例；正常卵巢上皮組織（正常組）15例，取自子宮良性腫瘤切除的卵巢。惡性組患者的年齡為20~66歲，平均年齡為47.525.43歲；術(shù)前均未行放、化療。 2.研究方法 應(yīng)用逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)（RT-PCR）方法檢測三組中MTDH mRNA及VEGF mRNA的表達(dá)情況。應(yīng)用免疫組織化學(xué)SP法檢測三組中MTDH蛋白及VEGF蛋白的表達(dá)情況。3.統(tǒng)計學(xué)方法 應(yīng)用SPSS17.0軟件對實(shí)驗(yàn)數(shù)據(jù)進(jìn)行統(tǒng)計學(xué)處理。計量資料的比較用x s表示，采用單因素方差分析；計數(shù)資料的比較采用χ2檢驗(yàn)進(jìn)行分析，相關(guān)性分析采用pearson列聯(lián)相關(guān)；以=0.05為檢驗(yàn)水準(zhǔn)。兩兩比較：檢驗(yàn)水準(zhǔn)=/比較次數(shù)=0.0167。 結(jié)果 1.MTDH mRNA在惡性組中的相對表達(dá)量為0.672±0.115，顯著高于良性組（0.324±0.041）及正常組（0.317±0.035），差異均有統(tǒng)計學(xué)意義（P0.0167)。 2.VEGF mRNA在惡性組中的相對表達(dá)量為0.714±0.129，顯著高于良性組（0.251±0.039）及正常組（0.243±0.031），差異均有統(tǒng)計學(xué)意義（P0.0167)。 3.MTDH蛋白在惡性組中的陽性表達(dá)率為69.0%，顯著高于良性組（20.0%）與正常組（13.3%），差異均有統(tǒng)計學(xué)意義（P0.0167)。 4.VEGF蛋白在惡性組中的陽性表達(dá)率為80.9%，顯著高于良性組（35.0%）與正常組（20.0%），差異均具有統(tǒng)計學(xué)意義（P0.0167)。 5.MTDH蛋白與VEGF蛋白在上皮性卵巢癌中的表達(dá)呈顯著正相關(guān)(rp=0.420,P0.01)。 6.MTDH mRNA、VEGF mRNA及兩者相對應(yīng)蛋白的表達(dá)與上皮性卵巢癌的臨床分期、淋巴結(jié)轉(zhuǎn)移有關(guān)（P0.05)，而與其病理類型及組織分化程度無關(guān)（P0.05）。 結(jié)論 1.MTDH在惡性組中的表達(dá)率顯著高于良性組及正常組，提示MTDH可能在上皮性卵巢癌的發(fā)生、發(fā)展中起重要作用。 2.MTDH高表達(dá)的上皮性卵巢癌組織中VEGF同樣高表達(dá)，兩者具有顯著正相關(guān)性，MTDH可能通過某種機(jī)制誘導(dǎo)VEGF的表達(dá)。 3.上皮性卵巢癌中MTDH的過表達(dá)提示患者的預(yù)后差，可能作為血管發(fā)生的重要誘導(dǎo)因子與VEGF協(xié)同參與上皮性卵巢癌的生長、轉(zhuǎn)移和擴(kuò)散。
[Abstract]:Ovarian cancer is one of the most common gynecological malignancy, although the survival rate in recent years has increased, but the majority is diagnosed at advanced stage, there is a close relationship between the overall 5 year survival rate is not more than 40%. tumor development and tumor angiogenesis, the growth of these new vessels in ovarian tumors, and metastasis play a major role in the diffusion process. Vascular endothelial growth factor (vascular endothelial, growthfactor, VEGF) can not only make the tumor vascular permeability increase in tumor cell invasion ability, but also can promote vascular endothelial cell proliferation, induce the formation of tumor angiogenesis, thus promoting the development of invasion and metastasis.
Metadherin (Metadherin, MTDH) gene known as astrocyte elevated gene 1 (astrocyteelevated gene1, AEG-1), is a human immunodeficiency virus type 1 (humanimmunodeficiency virus-1 HIV-1) infected glial cells of human embryonic astrocytes or by TNF alpha - induced, the expression product of MTDH. research has shown that MTDH is an oncogene is induced by angiogenic factor, in breast cancer, glioblastoma multiforme, malignant melanoma, renal cell carcinoma, endometrial carcinoma, colorectal cancer and breast cancer and other malignant tumors, play a major role in development and metastasis of tumor cells on the. Epithelial ovarian cancer research very little, the results are not the same, need further research. This study through the detection of RT-PCR and SP immunohistochemical method in different epithelial ovarian tissue in MTDH mRNA, VEGF and mRNA The expression of the corresponding protein and its role in ovarian epithelial tumor and its application value.
objective
Objective to investigate the expression of MTDH and VEGF in epithelial ovarian cancer and their relationship with the occurrence and development of epithelial ovarian cancer, and to analyze the correlation between the expression of MTDH protein and VEGF protein in epithelial ovarian cancer.
Materials and methods
1. research objects
From the Third Affiliated Hospital of Zhengzhou University from July 2010 to April 2013 in obstetrics and gynecology hospital underwent surgical resection of primary epithelial ovarian cancer (malignant group) 42 cases, including 25 cases of serous cystic carcinoma, 10 cases of mucinous cystic carcinoma, 7 cases of endometrioid carcinoma; benign ovarian epithelial tumors (benign group) in 20 cases; normal ovarian tissues (normal group) and 15 cases of benign ovarian tumor, taken from hysterectomy. Malignant patients aged 20~66 years old, the average age of 47.525.43 years; no preoperative radiotherapy and chemotherapy.
2. research methods
Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of MTDH mRNA and VEGF mRNA in three groups. The expression of MTDH protein and VEGF protein in three groups were detected by immunohistochemical SP method..3. statistics method was used.
Application of SPSS17.0 software for statistical analysis of experimental data. The measurement data that compared with x s, using the single factor analysis of variance; count data were compared using 2 test analysis, correlation analysis using Pearson correlation; the inspection standard is =0.05. 22: test level = / compare the number of =0.0167.
Result
The relative expression level of 1.MTDH mRNA in malignant group was 0.672 + 0.115, which was significantly higher than that in benign group (0.324 + 0.041) and normal group (0.317 + 0.035), the difference was statistically significant (P0.0167).
The relative expression level of 2.VEGF mRNA in malignant group was 0.714 + 0.129, which was significantly higher than that in benign group (0.251 + 0.039) and normal group (0.243 + 0.031), the difference was statistically significant (P0.0167).
The positive expression rate of 3.MTDH protein in the malignant group was 69%, which was significantly higher than that in the benign group (20%) and the normal group (13.3%), and the difference was statistically significant (P0.0167).
The positive expression rate of 4.VEGF protein in the malignant group was 80.9%, which was significantly higher than that in the benign group (35%) and the normal group (20%), and the difference was statistically significant (P0.0167).
The expression of 5.MTDH protein and VEGF protein in epithelial ovarian cancer is positively correlated (rp=0.420, P0.01).
The expressions of 6.MTDH mRNA, VEGF mRNA and their corresponding proteins were correlated with the clinical stage and lymph node metastasis of epithelial ovarian cancer (P0.05), but not related to their pathological types and histological differentiation (P0.05).
conclusion
The expression rate of 1.MTDH in the malignant group is significantly higher than that in the benign group and the normal group, suggesting that MTDH may play an important role in the development of epithelial ovarian cancer.
The expression of VEGF in 2.MTDH highly expressed epithelial ovarian cancer tissues is also highly expressed, and there is a significant positive correlation between them. MTDH may induce the expression of VEGF through some mechanism.
3., over expression of MTDH in epithelial ovarian cancer indicates poor prognosis. It may serve as an important inducer of angiogenesis and VEGF participate in the growth, metastasis and proliferation of epithelial ovarian cancer.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.31

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