本文選題：ARID1A基因 + CHK2基因��； 參考：《北京協(xié)和醫(yī)學(xué)院》2016年博士論文

【摘要】：背景：卵巢惡性腫瘤,也稱為卵巢癌,是女性生殖系統(tǒng)最常見的惡性腫瘤之一,發(fā)病率僅次于子宮頸癌而列居第二位,對(duì)婦女生命造成嚴(yán)重威脅。由于卵巢的胚胎發(fā)育、組織解剖及內(nèi)分泌功能較復(fù)雜,癥狀不典型,早期診斷極為困難。盡管人們對(duì)于卵巢癌的認(rèn)識(shí)在不斷加深,多種與卵巢癌發(fā)生發(fā)展相關(guān)的基因被人們所認(rèn)識(shí),但目前依然沒有令人滿意的標(biāo)記物可以用于卵巢癌的早期篩查和預(yù)后評(píng)估。目的：1.通過免疫組織化學(xué)分析獲得ARID1A基因和CHK2基因在卵巢內(nèi)膜樣癌中蛋白水平的表達(dá)情況；2.獲得ARID1A基因和CHK2基因在卵巢內(nèi)膜樣癌中的表達(dá)異常比率；3.分析以上兩種基因的表達(dá)與臨床分期的關(guān)系；4.分析ARID1A基因所表達(dá)蛋白在子宮內(nèi)膜異位癥及卵巢子宮內(nèi)膜樣癌中的表達(dá)情況,探究ARID1A基因與內(nèi)異癥相關(guān)卵巢癌的關(guān)系：5.進(jìn)一步明確CHK2基因在子宮內(nèi)膜樣癌中的蛋白表達(dá)異常比率,探究其與卵巢癌臨床分期及病理級(jí)別之間的關(guān)系。方法：選取2015-1至2016-1北京協(xié)和醫(yī)院婦科收治的術(shù)后病理診斷為卵巢子宮內(nèi)膜樣癌的患者,及1995-1至2016-3在北京協(xié)和醫(yī)院婦科診治的患有子宮內(nèi)膜異位癥,后患有卵巢癌,并因上述兩種疾病分別接受手術(shù)治療的患者,卵巢癌術(shù)后病理診斷需為卵巢子宮內(nèi)膜樣癌。對(duì)其卵巢子宮內(nèi)膜樣癌、子宮內(nèi)膜異位癥標(biāo)本及可能存在的不典型子宮內(nèi)膜異位癥進(jìn)行免疫組織化學(xué)染色通過進(jìn)行數(shù)據(jù)整理和分析獲得兩種基因在卵巢子宮內(nèi)膜樣癌中的表達(dá)情況。結(jié)果：1.ARID1A基因蛋白水平表達(dá)異常的比率為44%;CHK2基因蛋白水平表達(dá)缺失比率為36%;2.合并子宮內(nèi)膜異位癥患者中ARID1A基因蛋白表達(dá)異常比率為66.7%;3. ARID1A基因蛋白表達(dá)異常患者,化療后CA125恢復(fù)正常水平所需化療程數(shù)多于該基因?qū)?yīng)蛋白正常表達(dá)患者；4.CHK2基因表達(dá)蛋白水平異�；颊咴谀挲g、臨床分期、CA125水平、病理分級(jí)、淋巴結(jié)轉(zhuǎn)移情況、鉑類藥物耐藥比例、CA125恢復(fù)正常水平所需化療程數(shù)幾項(xiàng)臨床指標(biāo)的比較中,與CHK2基因蛋白表達(dá)水平正�；颊邿o明確的統(tǒng)計(jì)學(xué)差異;5. ARID1A基因的表達(dá)異常在卵巢子宮內(nèi)膜異位癥中即有發(fā)生。結(jié)論：1.在25例卵巢子宮內(nèi)膜樣癌患者中,ARID1A基因蛋白水平表達(dá)比率異常為44%；CHK2基因蛋白表達(dá)異常比率為36%,提示兩種基因蛋白異常表達(dá)與卵巢癌的形成有密切關(guān)系；2.對(duì)于合并子宮內(nèi)膜異位癥的患者,其ARID1A基因表達(dá)蛋白水平異常比率明顯升高,且在子宮內(nèi)膜異位癥中即有發(fā)生蛋白表達(dá)異常,提示ARID1A基因可能與子宮內(nèi)膜異位癥惡變相關(guān)并且可能在子宮內(nèi)膜異位癥惡變的早期即發(fā)揮作用；3. ARID1A基因表達(dá)蛋白水平異�；颊�,整體年齡及CA125水平有偏低趨勢,其CA125恢復(fù)正常水平所需化療程數(shù)多于該蛋白正常表達(dá)患者,提示ARID1A基因的異常表達(dá)對(duì)于鉑類藥物化療的敏感性有一定影響；4.CHK2基因不適合作為卵巢子宮內(nèi)膜樣癌預(yù)后的篩查指標(biāo)。
[Abstract]:Background: ovarian malignant tumor, also known as ovarian cancer, is one of the most common malignant tumors in the female reproductive system. The incidence of ovarian cancer is ranked the second only after cervical cancer. It is a serious threat to women's life. Because of ovarian embryo development, the anatomy and endocrine function are complex, the symptoms are not typical, early diagnosis is extremely difficult. The understanding of ovarian cancer is deepening, and many genes related to the development of ovarian cancer are recognized. However, there are still no satisfactory markers for early screening and prognostic evaluation of ovarian cancer. Objective: 1. the ARID1A and CHK2 genes in the ovarian endometrium were obtained by immunohistochemical analysis. The expression of protein level in cancer; 2. to obtain the abnormal rate of expression of ARID1A gene and CHK2 gene in ovarian endometrioid carcinoma; 3. to analyze the relationship between the expression of the above two genes and the clinical stages; 4. to analyze the expression of the protein expressed by the ARID1A gene in endometriosis and endometrioid carcinoma of the ovary and to explore the ARID1A base The relationship with ovarian cancer associated with endometriosis: 5. further clarify the abnormal protein expression ratio of CHK2 gene in endometrioid carcinoma, explore the relationship between the clinical stage and the pathological grade of ovarian cancer. Methods: select 2015-1 to 2016-1 of the gynecologic diagnosis of endometrioid carcinoma in the Department of gynecology in Peking Union Medical College Hospital. Patients with endometriosis and 1995-1 to 2016-3 in Peking Union Medical College Hospital were diagnosed with endometriosis, patients with ovarian cancer, and patients undergoing surgical treatment for the above two diseases. The pathological diagnosis of ovarian cancer after operation is ovarian endometrioid carcinoma. The endometrioid carcinoma of the ovary, endometriosis and possible existence of the ovarian endometrioid carcinoma. The expression of two genes in endometrioid carcinoma in ovarian endometrium was obtained by immunohistochemical staining of atypical endometriosis. Results: the rate of abnormal expression of 1.ARID1A gene protein was 44%, and the loss ratio of CHK2 gene protein was 36%; 2. combined with endometriosis. The rate of abnormal expression of ARID1A gene protein was 66.7%, and the patients with abnormal expression of 3. ARID1A gene protein were more than the normal expression of the corresponding protein after the chemotherapy of CA125, and the patients with abnormal 4.CHK2 gene protein level were in age, clinical stage, CA125 level, pathological grade, lymph node metastasis. The proportion of platinum drug resistance and the number of clinical indicators needed for the recovery of the normal level of CA125 were compared with those of the normal CHK2 gene protein expression level, and the abnormal expression of the 5. ARID1A gene occurred in ovarian endometriosis. Conclusion: 1. in 25 cases of ovarian endometrioid carcinoma. The abnormal expression ratio of ARID1A gene protein was 44%, and the abnormal expression rate of CHK2 gene protein was 36%, suggesting that the abnormal expression of two gene proteins was closely related to the formation of ovarian cancer. 2. for patients with endometriosis, the abnormal ratio of ARID1A gene expression level was significantly higher and endometriosis in endometriosis. There is an abnormal expression of protein in the disease, suggesting that ARID1A gene may be associated with endometriosis malignancy and may play a role in the early stage of endometriosis malignancy; 3. ARID1A gene expression protein level abnormal patients, the overall age and CA125 level have a low trend, and the number of chemotherapy courses required for the recovery of the normal level of CA125 More than the normal expression of this protein, it is suggested that the abnormal expression of ARID1A gene has some influence on the chemo sensitivity of platinum drugs, and the 4.CHK2 gene is not suitable as a screening indicator for the prognosis of ovarian endometrioid carcinoma.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.31

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