本文選題：宮頸上皮內瘤變 + 宮頸癌��； 參考：《河北大學》2017年碩士論文

【摘要】：目的:通過對病理診斷異常的宮頸病變組織檢測MAGE-A3、MAGE-A9蛋白及基因的表達情況,并與正常組織進行對比。研究MAGE-A3、MAGE-A9與宮頸上皮內瘤變及宮頸癌的發(fā)生和發(fā)展的關系,從而對宮頸病變的診斷和治療提供一定的理論依據(jù),進而研究出切實可行的治療方案。方法:選取我院2009年-2015年收治的宮頸病變患者,其中宮頸上皮內瘤變(CINⅢ)40例,宮頸癌Ia~b期(FIGO分期)60例,宮頸癌IIa期(FIGO分期)24例,正常宮頸40例。所有患者均進行手術治療,查閱患者病歷資料,結合患者的臨床病理資料進行分析。調取所有的患者病理組織蠟塊,行免疫組織化學染色,光鏡下觀察MAGE-A3、MAGE-A9表達情況。同時收集2015年-2016年我院手術室切下新鮮手術組織,運用實時熒光PCR方法檢測:15例正常宮頸,15例CINⅢ,20例宮頸癌組織中,MAGE-A3、MAGE-A9基因的表達情況。運用Western Blot方法檢測15例正常宮頸,15例CINⅢ組織,20例宮頸癌組織中MAGE-A3、MAGE-A9蛋白的表達情況。結果:1.免疫組化法顯示:MAGE-A3蛋白主要定位在細胞質內,且表達水平隨著宮頸病變程度的加重而逐漸升高。MAGE-A3在正常宮頸、CINⅢ和宮頸癌組織中的陽性表達率分別為5.00%、15.00%、48.81%,三者陽性表達呈逐漸上升的趨勢,統(tǒng)計學分析發(fā)現(xiàn),宮頸癌組分別與CINⅢ組及正常對照組相比,MAGE-A3的表達明顯升高,均有顯著性差異(P0.01);但是,正常組與CINⅢ組相比較,差異無統(tǒng)計學意義(P0.05);同時研究顯示MAGE-A3的表達水平與宮頸癌的臨床分期、病理分級、淋巴結轉移及高危型HPV感染之間差異均有統(tǒng)計學意義(P0.05)。MAGE-A9蛋白主要定位在細胞質內,MAGE-A9在正常宮頸、CINⅢ和宮頸癌組織中的陽性表達率分別為7.50%、17.50%、55.95%,三者陽性表達呈逐漸上升的趨勢,統(tǒng)計學分析發(fā)現(xiàn),宮頸癌組分別與CINⅢ組及正常對照組相比,MAGE-A9的表達明顯升高,均有顯著性差異(p0.01);但是,正常組與CINⅢ組相比較,差異無統(tǒng)計學意義(P0.05);同時研究顯示MAGE-A9的表達水平與宮頸癌的臨床分期、各病理分級以及有無淋巴結轉移之間差異均有統(tǒng)計學意義(p0.05)。2.實時熒光定量PCR法顯示:(1)以GAPDH mRNA為內參照標準,正常宮頸、CINⅢ及宮頸癌組織中MAGE-A3 mRNA的相對表達水平分別為0.184±0.069,0.221±0.086與0.702±0.145。MAGE-A3mRNA的相對表達量在宮頸癌中明顯高于CINⅢ及正常組織,宮頸癌組與正常組及CINⅢ組間差異均有統(tǒng)計學意義(P0.05),而正常組與CINⅢ組之間差異無統(tǒng)計學意義(P0.05)(2)以GAPDH mRNA為內參照標準,正常宮頸、CINⅢ及宮頸癌組織中MAGE-A9 mRNA的相對表達水平分別為0.182±0.062,0.234±0.087與0.642±0.150,其中宮頸癌組織中的MAGE-A9表達量明顯高于CIN及正常組織,宮頸癌組與正常組及CINⅢ組間差異均有統(tǒng)計學意義(P0.05),而正常組與CINⅢ組之間差異無統(tǒng)計學意義(P0.05)3.Western bloting蛋白印跡顯示:(1)MAGE-A3的灰度隨著宮頸組織病變程度的加重逐漸加深,正常宮頸、CINⅢ及宮頸癌組織中MAGE-A3蛋白的相對表達水平分別為0.943±0.178、1.035±0.139、1.977±0.105。宮頸癌組織中的MAGE-A9蛋白的相對表達量明顯高于CINⅢ及正常宮頸組織,差異均有統(tǒng)計學意義(P0.05),而正常組與CINⅢ組之間差異無統(tǒng)計學意義(P0.05)。(2)MAGE-A9的灰度隨著宮頸組織病變程度的加重逐漸加深,正常宮頸、CIN及宮頸癌組織中MAGE-A9蛋白的相對表達水平分別為0.857±0.315、0.909±0.526、1.882±0.179。宮頸癌組織中的MAGE-A9蛋白的相對表達量明顯高于CINⅢ及正常宮頸組織,差異均有統(tǒng)計學意義(P0.05),而正常組與CINⅢ組之間差異無統(tǒng)計學意義(P0.05)。結論:1、MAGE-A3的過表達與宮頸癌的發(fā)生發(fā)展緊密相關,而且MAGE-A3的過量表達與宮頸癌的臨床分期,病理分級及淋巴轉移及高危HPV感染緊密相關,而與年齡及癌癥類型沒有明顯關聯(lián),MAGE-A3有可能成為宮頸疾病早期診斷、宮頸癌治療的重要腫瘤標記物。MAGE-A3可能成為宮頸癌生物治療提供理想的靶點,對于進一步了解宮頸癌生物學行為判斷預后有很重要的臨床應用價值。2、MAGE-A9的過表達與宮頸癌發(fā)生發(fā)展密切相關,且MAGE-A9的過量表達與宮頸癌的臨床分期、病理分級及有無淋巴轉移有關,MAGE-A9有可能成為宮頸疾病早期診斷、宮頸癌治療的重要腫瘤標記物。MAGE-A9可能成為宮頸癌生物治療提供理想的靶點,MAGE-A9對于進一步了解宮頸癌生物學行為判斷預后有很重要的臨床應用價值。
[Abstract]:Objective: to detect the expression of MAGE-A3, MAGE-A9 protein and gene in pathological diagnosis of cervical lesions, and to compare with normal tissues and study the relationship between MAGE-A3, MAGE-A9 and cervical intraepithelial neoplasia and the occurrence and development of cervical cancer, so as to provide a theoretical basis for the diagnosis and treatment of cervical lesions. Methods: a practical treatment scheme was taken. Methods: selected patients with cervical lesions admitted in our hospital in -2015 2009, 40 cases of cervical intraepithelial neoplasia (CIN III), 60 cases of Ia~b stage (FIGO staging) of cervical cancer, 24 cases of IIa stage (FIGO stage) of cervical cancer and 40 cases of normal cervix. All patients were treated with surgical treatment, consult the patient's medical records, combined with patient's presence. The pathological data of the bed were analyzed. All the pathological tissue wax blocks were collected, the immunohistochemical staining was performed and the expression of MAGE-A3 and MAGE-A9 was observed under light microscope. At the same time, the fresh surgical tissues were cut down in the operation room of our hospital in 2015 -2016, and the real time fluorescence PCR method was used to detect 15 cases of normal cervix, 15 cases of CIN III, and 20 cases of cervical cancer tissues, MAGE- The expression of A3, MAGE-A9 gene. The expression of MAGE-A3 and MAGE-A9 in 15 cases of normal cervix, 15 cases of CIN III tissue and 20 cases of cervical cancer were detected by Western Blot. Results: 1. immunohistochemistry showed that MAGE-A3 protein was mainly located in the cytoplasm, and the level of expression gradually increased with the severity of cervical lesions. The positive expression rate of A3 in normal cervix, CIN III and cervical cancer tissues was 5%, 15%, 48.81%, and the positive expression of three was gradually rising. The statistical analysis showed that the expression of MAGE-A3 in the cervical cancer group was significantly higher than that of the CIN group and the normal control group (P0.01), but the normal group and the CIN III group were significantly different. The difference was not statistically significant (P0.05). At the same time, the study showed that the expression level of MAGE-A3 and the clinical stage of cervical cancer, pathological classification, lymph node metastasis and high risk HPV infection were statistically significant (P0.05).MAGE-A9 protein was mainly located in the cytoplasm, MAGE-A9 was in the normal cervix, CIN III and cervical cancer tissues. The positive expression rates were 7.50%, 17.50%, 55.95% and three, respectively. The statistical analysis showed that the expression of MAGE-A9 was significantly higher in the cervical cancer group than in the CIN III group and the normal control group (P0.01), but there was no significant difference between the normal group and the CIN group (P0.05). The results showed that the expression level of MAGE-A9 and the clinical stage of cervical cancer, the pathological grades and the lymph node metastasis were statistically significant (P0.05).2. real-time fluorescence quantitative PCR method showed: (1) the relative expression level of MAGE-A3 mRNA in normal cervix, CIN III and cervical cancer tissues was 0.184 +, respectively, with GAPDH mRNA as the internal reference standard. The relative expression of 0.069,0.221 + 0.086 and 0.702 + 0.145.MAGE-A3mRNA in cervical cancer was significantly higher than that of CIN III and normal tissue. The difference between the cervical cancer group and the normal group and the group CIN III was statistically significant (P0.05), while the difference between the normal group and the CIN III group was not statistically significant (P0.05) (2) with GAPDH mRNA as the internal reference standard, normal cervix, CIN, and CIN. The relative expression level of MAGE-A9 mRNA in cervical cancer tissues was 0.182 + 0.062,0.234 + 0.087 and 0.642 + 0.150 respectively. The expression of MAGE-A9 in cervical cancer tissues was significantly higher than that of CIN and normal tissues. The difference between the cervical cancer group and the normal group and the CIN III group was statistically significant (P0.05), but there was no difference between the normal group and the CIN group group III group. The study significance (P0.05) 3.Western bloting Western blot showed: (1) the gray level of MAGE-A3 gradually deepened with the severity of cervical tissue lesion, and the relative expression level of MAGE-A3 protein in normal cervix, CIN III and cervical cancer tissues was relative expression of MAGE-A9 protein in 0.943 + 0.178,1.035 + 0.139,1.977 + 0.105. cervical cancer tissues The difference was significantly higher than that of CIN III and normal cervical tissue (P0.05), but there was no significant difference between the normal group and the CIN group (P0.05). (2) the gray level of MAGE-A9 gradually deepened with the severity of cervical tissue lesion, and the relative expression level of MAGE-A9 protein in normal cervix, CIN and cervical cancer tissues was 0.857 + 0, respectively. The relative expression of MAGE-A9 protein in.315,0.909 + 0.526,1.882 + 0.179. cervical cancer tissues was significantly higher than that of CIN III and normal cervical tissue (P0.05), but there was no significant difference between the normal group and the CIN group (P0.05). Conclusion: 1, the overexpression of MAGE-A3 is closely related to the development of cervical cancer, and the MAGE- is closely related to the development of cervical cancer, and MAGE- is closely related to the occurrence and development of cervical cancer, and MAGE-, and MAGE- The overexpression of A3 is closely related to the clinical stage of cervical cancer, pathological grading, lymphatic metastasis and high risk HPV infection, but not associated with age and cancer type. MAGE-A3 may be an early diagnosis of cervical disease. The important tumor marker for cervical cancer treatment can be an ideal target for the biological treatment of cervical cancer. To further understand the prognosis of cervical cancer biological behavior is of great clinical value.2, the overexpression of MAGE-A9 is closely related to the development of cervical cancer, and the overexpression of MAGE-A9 is related to the clinical stage of cervical cancer, pathological classification and lymphatic metastasis. MAGE-A9 may be the early diagnosis of cervical disease and cervical cancer. The important tumor marker,.MAGE-A9, may be an ideal target for the biological treatment of cervical cancer. MAGE-A9 is of great clinical value for the further understanding of the prognosis of cervical cancer biological behavior.
【學位授予單位】：河北大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R737.33

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