MTDH、VEGF在上皮性卵巢癌中的表达及临床意义

发布时间：2018-03-30 22:15

本文选题：上皮性卵巢癌　切入点：MTDH　出处：《郑州大学》2014年硕士论文

【摘要】：上皮性卵巢癌是妇科常见的恶性肿瘤之一，其生存率近年来虽然已有所提高，但大多数确诊时已为晚期，5年总体生存率仍未超过40％。肿瘤的发生发展与肿瘤新生血管的形成有密切关系，这些新生血管在卵巢肿瘤的生长、转移和扩散过程中均发挥重大作用。血管内皮生长因子（vascular endothelial growthfactor，VEGF）不仅能使肿瘤血管的通透性增加，肿瘤细胞浸润能力增强，而且能促进血管内皮细胞的增生，诱导肿瘤新生血管的形成，从而促进肿瘤的发展和侵袭转移。异黏蛋白（Metadherin，MTDH）基因又名星形胶质细胞升高基因1（astrocyteelevated gene1，AEG-1），是由人类免疫缺陷病毒1型（humanimmunodeficiency virus-1，HIV-1）感染人类胚胎性星形胶质细胞或由肿瘤坏死因子-ɑ诱导产生的，其表达产物为MTDH。有研究表明MTDH既是一种致癌基因，又是血管形成的诱导因子，，其在乳腺癌、多形性胶质母细胞瘤、恶性黑色素瘤、肾细胞癌、子宫内膜癌、结直肠癌及胸腺癌等多种恶性肿瘤的发生、发展及瘤细胞转移中发挥重大作用。有关其在上皮性卵巢癌中的研究甚少，其结果也不尽相同，需更进一步研究。本研究通过RT-PCR及免疫组织化学SP法检测不同卵巢上皮组织中MTDH mRNA、VEGF mRNA及两者对应蛋白的表达，探讨其在卵巢上皮性肿瘤中的作用及应用价值。目的探讨MTDH、VEGF在上皮性卵巢癌中的表达及两者与上皮性卵巢癌发生发展的关系；分析上皮性卵巢癌中MTDH蛋白及VEGF蛋白表达之间的相关性。材料与方法 1.研究对象收集郑州大学第三附属医院妇产科2010年7月到2013年4月住院行手术切除的原发性上皮性卵巢癌组织（恶性组）42例，其中浆液性囊性癌25例、粘液性囊性癌10例、子宫内膜样癌7例；卵巢良性上皮性肿瘤组织（良性组）20例；正常卵巢上皮组织（正常组）15例，取自子宫良性肿瘤切除的卵巢。恶性组患者的年龄为20~66岁，平均年龄为47.525.43岁；术前均未行放、化疗。 2.研究方法应用逆转录-聚合酶链反应（RT-PCR）方法检测三组中MTDH mRNA及VEGF mRNA的表达情况。应用免疫组织化学SP法检测三组中MTDH蛋白及VEGF蛋白的表达情况。3.统计学方法应用SPSS17.0软件对实验数据进行统计学处理。计量资料的比较用x s表示，采用单因素方差分析；计数资料的比较采用χ2检验进行分析，相关性分析采用pearson列联相关；以=0.05为检验水准。两两比较：检验水准=/比较次数=0.0167。结果 1.MTDH mRNA在恶性组中的相对表达量为0.672±0.115，显著高于良性组（0.324±0.041）及正常组（0.317±0.035），差异均有统计学意义（P0.0167)。 2.VEGF mRNA在恶性组中的相对表达量为0.714±0.129，显著高于良性组（0.251±0.039）及正常组（0.243±0.031），差异均有统计学意义（P0.0167)。 3.MTDH蛋白在恶性组中的阳性表达率为69.0%，显著高于良性组（20.0%）与正常组（13.3%），差异均有统计学意义（P0.0167)。 4.VEGF蛋白在恶性组中的阳性表达率为80.9%，显著高于良性组（35.0%）与正常组（20.0%），差异均具有统计学意义（P0.0167)。 5.MTDH蛋白与VEGF蛋白在上皮性卵巢癌中的表达呈显著正相关(rp=0.420,P0.01)。 6.MTDH mRNA、VEGF mRNA及两者相对应蛋白的表达与上皮性卵巢癌的临床分期、淋巴结转移有关（P0.05)，而与其病理类型及组织分化程度无关（P0.05）。结论 1.MTDH在恶性组中的表达率显著高于良性组及正常组，提示MTDH可能在上皮性卵巢癌的发生、发展中起重要作用。 2.MTDH高表达的上皮性卵巢癌组织中VEGF同样高表达，两者具有显著正相关性，MTDH可能通过某种机制诱导VEGF的表达。 3.上皮性卵巢癌中MTDH的过表达提示患者的预后差，可能作为血管发生的重要诱导因子与VEGF协同参与上皮性卵巢癌的生长、转移和扩散。
[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.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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