ARHI基因启动子甲基化与卵巢癌发生的关系

发布时间：2018-05-04 16:27

本文选题：卵巢癌 + ARHI基因　；参考：《新乡医学院》2014年硕士论文

【摘要】：背景卵巢癌的发生率位于妇科非良性肿瘤的第三位,但其存活率却最低。因卵巢在盆腔位置较深,卵巢癌患者大多早期症状不典型,所以及时发现并给予有效的治疗非常困难,约60%-70%的卵巢癌患者确诊时已到临床晚期。近年来,卵巢癌的研究一直是妇科肿瘤研究中集中点,虽然经过无数人的努力,使得手术方式不断地改进,并研发出了新型的化疗药物,总结了更先进的化疗方案。这些虽然一定程度上提高了晚期卵巢癌患者的生存质量,然而其5年生存率依旧波动在25%-35%。当今卵巢癌的发病原因和机理尚不明确,缺乏特异敏感的早期诊断方法。故,揭示卵巢癌的发生、进展机理在其早期明确诊断、及时有效的治疗具有重要意义。 ARHI基因是现今发现的一个与妇科肿瘤密切相关的因启动子甲基化而失活的重要抑癌基因。本实验用甲基化PCR法对15例正常卵巢组织,15例良性卵巢肿瘤组织,20例卵巢癌组织中ARHI基因启动子甲基化进行检测,用免疫组化SP法检测上述标本中VEGF蛋白表达的情况。以阐明ARHI基因甲基化及VEGF高表达在卵巢癌发生发展中的机制,为卵巢癌的治疗寻找新的作用点。目的研究ARHI基因启动子甲基化、VEGF蛋白在卵巢癌组织中的表达,探讨ARHI基因启动子甲基化在卵巢癌形成过程中的影响及意义。方法 1.研究对象：收集2009年5月-2013年6月在濮阳市人民医院病理科存档的手术切除的卵巢上皮性组织蜡块50例,其中包括正常卵巢组织15例(A组),良性卵巢肿瘤组织15例(B组),卵巢癌20例(浆液性囊腺癌组织13例,黏液性囊腺癌组织7例)(C组)。卵巢癌病人年龄为20-65岁,中位年龄为46岁。所有患者术前均未接受放疗或化疗。15例正常卵巢组织取自全子宫加双附件切除术的正常侧卵巢。 2.研究方法：用免疫组化法检测VEGF蛋白在正常卵巢组织、良性卵巢肿瘤组织及卵巢癌组织中表达的情况。用MS-PCR法(甲基化特异的聚合酶链反应)检测正常卵巢组织、良性卵巢肿瘤组织及卵巢癌组织中ARHI基因启动子甲基化情况。 3.统计学方法：应用SPSS16.0统计软件进行分析,免疫组化所有数据均采用均值±标准差(x±s)表示。甲基化结果用χ2检验进行分析。显著性水准α=0.05。结果 1.良性卵巢肿瘤组织(B组)、卵巢癌组织(C组)中ARHI基因启动子甲基化频率分别为：14.3%,75%。卵巢癌组织中的甲基化率明显高于良性卵巢肿瘤组织,B、C两组之间差别有统计学意义(χ=12.126,P0.05)。 2. VEGF蛋白在正常卵巢组织表达为阴性；在良性卵巢肿瘤组织中表现为弱阳性,阳性表达率为7/15(46.7%)；在卵巢癌组织中表达增强,阳性表达率为14/20(70.0%)为强阳性。(χ2=24.126,P0.001)。结论 1.卵巢癌组织中ARHI基因DNA启动子区存在甲基化状态,这可能在卵巢癌的发生机制中起着重要的作用。 2. VEGF蛋白的异常高表达参与了卵巢癌的发生发展。
[Abstract]:Background The incidence of ovarian cancer is the third most common in gynecological non-benign tumors, but its survival rate is the lowest. Because the ovary is deep in the pelvic cavity and most of the early symptoms of ovarian cancer patients are not typical, it is very difficult to find and give effective treatment in time. About 60-70% of the patients with ovarian cancer have reached the clinical advanced stage by the time of diagnosis. In recent years, the research of ovarian cancer has been the focus of gynecological cancer research, although through the efforts of countless people, the operation mode has been improved, and a new type of chemotherapy drugs has been developed, and a more advanced chemotherapy scheme has been summarized. Although these may improve the quality of life in patients with advanced ovarian cancer, the 5-year survival rate fluctuates from 25 to 35. At present, the etiology and mechanism of ovarian cancer are not clear, and there is no specific and sensitive method for early diagnosis. Therefore, it is important to reveal the occurrence of ovarian cancer, the mechanism of progression in its early diagnosis, timely and effective treatment. ARHI gene is an important tumor suppressor gene inactivated by promoter methylation, which is closely related to gynecologic tumors. The methylation of ARHI promoter was detected by methylation PCR method in 15 normal ovarian tissues and 15 benign ovarian tumor tissues. The expression of VEGF protein was detected by immunohistochemical SP method. In order to elucidate the mechanism of ARHI gene methylation and VEGF overexpression in the development of ovarian cancer and find a new therapeutic point for ovarian cancer. Purpose To investigate the expression of ARHI gene promoter methylation protein in ovarian cancer and to explore the effect of ARHI promoter methylation on the formation of ovarian cancer. Method 1. Participants: from May 2009 to June 2013, 50 cases of ovarian epithelial tissue wax were collected and archived in the Department of Pathology of Puyang people's Hospital, Puyang City. There were 15 cases of normal ovarian tissues in group A, 15 cases of benign ovarian tumors in group B, and 20 cases of ovarian carcinoma (serous cystadenocarcinoma in 13 cases, mucinous cystadenocarcinoma in 7 cases). The age of ovarian cancer patients was 20-65 years old and the median age was 46 years. All patients received no radiotherapy or chemotherapy before operation. 15 cases of normal ovarian tissue were obtained from the normal ovary after hysterectomy. 2. Methods: immunohistochemical method was used to detect the expression of VEGF protein in normal ovarian tissues, benign ovarian tumor tissues and ovarian cancer tissues. Methylation-specific polymerase chain reaction (MS-PCR) was used to detect the methylation of ARHI promoter in normal ovarian tissues, benign ovarian tumor tissues and ovarian cancer tissues. 3. Statistical methods: all the immunohistochemical data were expressed by mean 卤standard deviation (x 卤s). The methylation results were analyzed by 蠂 2 test. The significant level of 伪 -0. 05. Result 1. The methylation frequency of ARHI gene promoter in benign ovarian tumor tissue group B and ovarian cancer tissue group C) was respectively: 1. 14. 3% and 75%. The methylation rate in ovarian cancer tissues was significantly higher than that in benign ovarian tumor tissues (蠂 ~ (2) 12.126) (P < 0.05). 2. The expression of VEGF protein was negative in normal ovarian tissues, weakly positive in benign ovarian neoplasms with a positive rate of 7 / 15 / 46.7%, and increased in ovarian cancer tissues with a positive expression rate of 14 / 2070.0. Conclusion 1. The methylation of the DNA promoter of ARHI gene may play an important role in the pathogenesis of ovarian cancer. 2. Abnormal overexpression of VEGF protein is involved in the development of ovarian cancer.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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