本文選題：卵巢癌 + ARHI基因�。� 參考：《新鄉(xiāng)醫(yī)學(xué)院》2014年碩士論文

【摘要】：背景 卵巢癌的發(fā)生率位于婦科非良性腫瘤的第三位,但其存活率卻最低。因卵巢在盆腔位置較深,卵巢癌患者大多早期癥狀不典型,所以及時(shí)發(fā)現(xiàn)并給予有效的治療非常困難,約60%-70%的卵巢癌患者確診時(shí)已到臨床晚期。近年來,卵巢癌的研究一直是婦科腫瘤研究中集中點(diǎn),雖然經(jīng)過無數(shù)人的努力,使得手術(shù)方式不斷地改進(jìn),并研發(fā)出了新型的化療藥物,總結(jié)了更先進(jìn)的化療方案。這些雖然一定程度上提高了晚期卵巢癌患者的生存質(zhì)量,然而其5年生存率依舊波動在25%-35%。當(dāng)今卵巢癌的發(fā)病原因和機(jī)理尚不明確,缺乏特異敏感的早期診斷方法。故,揭示卵巢癌的發(fā)生、進(jìn)展機(jī)理在其早期明確診斷、及時(shí)有效的治療具有重要意義。 ARHI基因是現(xiàn)今發(fā)現(xiàn)的一個(gè)與婦科腫瘤密切相關(guān)的因啟動子甲基化而失活的重要抑癌基因。本實(shí)驗(yàn)用甲基化PCR法對15例正常卵巢組織,15例良性卵巢腫瘤組織,20例卵巢癌組織中ARHI基因啟動子甲基化進(jìn)行檢測,用免疫組化SP法檢測上述標(biāo)本中VEGF蛋白表達(dá)的情況。以闡明ARHI基因甲基化及VEGF高表達(dá)在卵巢癌發(fā)生發(fā)展中的機(jī)制,為卵巢癌的治療尋找新的作用點(diǎn)。 目的 研究ARHI基因啟動子甲基化、VEGF蛋白在卵巢癌組織中的表達(dá),探討ARHI基因啟動子甲基化在卵巢癌形成過程中的影響及意義。 方法 1.研究對象：收集2009年5月-2013年6月在濮陽市人民醫(yī)院病理科存檔的手術(shù)切除的卵巢上皮性組織蠟塊50例,其中包括正常卵巢組織15例(A組),良性卵巢腫瘤組織15例(B組),卵巢癌20例(漿液性囊腺癌組織13例,黏液性囊腺癌組織7例)(C組)。卵巢癌病人年齡為20-65歲,中位年齡為46歲。所有患者術(shù)前均未接受放療或化療。15例正常卵巢組織取自全子宮加雙附件切除術(shù)的正常側(cè)卵巢。 2.研究方法：用免疫組化法檢測VEGF蛋白在正常卵巢組織、良性卵巢腫瘤組織及卵巢癌組織中表達(dá)的情況。用MS-PCR法(甲基化特異的聚合酶鏈反應(yīng))檢測正常卵巢組織、良性卵巢腫瘤組織及卵巢癌組織中ARHI基因啟動子甲基化情況。 3.統(tǒng)計(jì)學(xué)方法：應(yīng)用SPSS16.0統(tǒng)計(jì)軟件進(jìn)行分析,免疫組化所有數(shù)據(jù)均采用均值±標(biāo)準(zhǔn)差(x±s)表示。甲基化結(jié)果用χ2檢驗(yàn)進(jìn)行分析。顯著性水準(zhǔn)α=0.05。 結(jié)果 1.良性卵巢腫瘤組織(B組)、卵巢癌組織(C組)中ARHI基因啟動子甲基化頻率分別為：14.3%,75%。卵巢癌組織中的甲基化率明顯高于良性卵巢腫瘤組織,B、C兩組之間差別有統(tǒng)計(jì)學(xué)意義(χ=12.126,P0.05)。 2. VEGF蛋白在正常卵巢組織表達(dá)為陰性；在良性卵巢腫瘤組織中表現(xiàn)為弱陽性,陽性表達(dá)率為7/15(46.7%)；在卵巢癌組織中表達(dá)增強(qiáng),陽性表達(dá)率為14/20(70.0%)為強(qiáng)陽性。(χ2=24.126,P0.001)。 結(jié)論 1.卵巢癌組織中ARHI基因DNA啟動子區(qū)存在甲基化狀態(tài),這可能在卵巢癌的發(fā)生機(jī)制中起著重要的作用。 2. VEGF蛋白的異常高表達(dá)參與了卵巢癌的發(fā)生發(fā)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 鹵standard deviation (x 鹵s). The methylation results were analyzed by 蠂 2 test. The significant level of 偽 -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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.31

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