卵巢子宫内膜样癌细胞中ARID1A及CHK2基因蛋白水平表达情况检测

发布时间：2018-05-31 11:19

本文选题：ARID1A基因 + CHK2基因　；参考：《北京协和医学院》2016年博士论文

【摘要】：背景：卵巢恶性肿瘤,也称为卵巢癌,是女性生殖系统最常见的恶性肿瘤之一,发病率仅次于子宫颈癌而列居第二位,对妇女生命造成严重威胁。由于卵巢的胚胎发育、组织解剖及内分泌功能较复杂,症状不典型,早期诊断极为困难。尽管人们对于卵巢癌的认识在不断加深,多种与卵巢癌发生发展相关的基因被人们所认识,但目前依然没有令人满意的标记物可以用于卵巢癌的早期筛查和预后评估。目的：1.通过免疫组织化学分析获得ARID1A基因和CHK2基因在卵巢内膜样癌中蛋白水平的表达情况；2.获得ARID1A基因和CHK2基因在卵巢内膜样癌中的表达异常比率；3.分析以上两种基因的表达与临床分期的关系；4.分析ARID1A基因所表达蛋白在子宫内膜异位症及卵巢子宫内膜样癌中的表达情况,探究ARID1A基因与内异症相关卵巢癌的关系：5.进一步明确CHK2基因在子宫内膜样癌中的蛋白表达异常比率,探究其与卵巢癌临床分期及病理级别之间的关系。方法：选取2015-1至2016-1北京协和医院妇科收治的术后病理诊断为卵巢子宫内膜样癌的患者,及1995-1至2016-3在北京协和医院妇科诊治的患有子宫内膜异位症,后患有卵巢癌,并因上述两种疾病分别接受手术治疗的患者,卵巢癌术后病理诊断需为卵巢子宫内膜样癌。对其卵巢子宫内膜样癌、子宫内膜异位症标本及可能存在的不典型子宫内膜异位症进行免疫组织化学染色通过进行数据整理和分析获得两种基因在卵巢子宫内膜样癌中的表达情况。结果：1.ARID1A基因蛋白水平表达异常的比率为44%;CHK2基因蛋白水平表达缺失比率为36%;2.合并子宫内膜异位症患者中ARID1A基因蛋白表达异常比率为66.7%;3. ARID1A基因蛋白表达异常患者,化疗后CA125恢复正常水平所需化疗程数多于该基因对应蛋白正常表达患者；4.CHK2基因表达蛋白水平异常患者在年龄、临床分期、CA125水平、病理分级、淋巴结转移情况、铂类药物耐药比例、CA125恢复正常水平所需化疗程数几项临床指标的比较中,与CHK2基因蛋白表达水平正常患者无明确的统计学差异;5. ARID1A基因的表达异常在卵巢子宫内膜异位症中即有发生。结论：1.在25例卵巢子宫内膜样癌患者中,ARID1A基因蛋白水平表达比率异常为44%；CHK2基因蛋白表达异常比率为36%,提示两种基因蛋白异常表达与卵巢癌的形成有密切关系；2.对于合并子宫内膜异位症的患者,其ARID1A基因表达蛋白水平异常比率明显升高,且在子宫内膜异位症中即有发生蛋白表达异常,提示ARID1A基因可能与子宫内膜异位症恶变相关并且可能在子宫内膜异位症恶变的早期即发挥作用；3. ARID1A基因表达蛋白水平异常患者,整体年龄及CA125水平有偏低趋势,其CA125恢复正常水平所需化疗程数多于该蛋白正常表达患者,提示ARID1A基因的异常表达对于铂类药物化疗的敏感性有一定影响；4.CHK2基因不适合作为卵巢子宫内膜样癌预后的筛查指标。
[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.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.31

【相似文献】