BRCA1、BRCA2、RAD51和FANCD2在上皮性卵巢癌中的表达及其与临床病理特征的关系

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摘要目的:探讨DNA双链断裂的同源重组修复相关的蛋白乳腺癌易感1（BRCA1）、乳腺癌易感2（BRCA2）、DNA修复蛋白RAD51和范可尼贫血D2蛋白（FANCD2）在卵巢癌组织中的表达及其与临床病理特征的关系。方法:收集上皮性卵巢癌（EOC）患者的临床癌组织样本共84例和正常卵巢组织6例，采用免疫组化法检测BRCA1、BRCA2、RAD51、FANCD2蛋白的表达。通过GEPIA分析TCGA数据库中4种基因在EOC组织中的表达以及它们之间的相关性。使用Ualcan分析TCGA数据库中4种基因在EOC组织中的表达水平与临床病理特征的关系。结果:免疫组化检测结果表明，BRCA2、RAD51和FANCD2蛋白在EOC组织中的阳性表达率显著高于正常卵巢组织（均P＜0.05）。经GEPIA对TCGA数据库分析，BRCA1、BRCA2、RAD51和FANCD2的mRNA表达在EOC组织中显著上升，且两两之间均呈明显正相关。经Ualcan对TCGA数据库分析，BRCA1 mRNA在41岁以上的患者中表达显著增高；且4种基因在2级（肿瘤组织学分级）以上的肿瘤中均表达较高，RAD51 mRNA在3级肿瘤中的表达明显高于2级肿瘤；FANCD2 mRNA在非洲裔人种中的表达显著高于白种人；TP53突变EOC组织中BRCA1、RAD51和FANCD2的mRNA表达显著高于未突变EOC组织。结论:EOC组织中BRCA2、FANCD2和RAD51等蛋白和mRNA表达显著升高，有可能成为卵巢癌诊疗的生物标志物。

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	刘兰兰
	王志新
	袁思锐
	石春燕
	卢子文
	胡兴
	刘晗青
	屠志刚

关键词 ：乳腺癌易感1, 乳腺癌易感2, RAD51, 范可尼贫血D2蛋白, 上皮性卵巢癌, 免疫组化

Abstract：Objective: To explore the protein expression of homologous recombination repair genes for DNA doublestrand breaks, such as breast cancer susceptibility protein 1 (BRCA1), breast cancer susceptibility protein 2 (BRCA2), DNA repair protein RAD51 and Fanconi anemia D2 protein (FANCD2), in ovarian cancer tissues and correlation with clinicopathological characteristics. Methods: Paraffin sections of 84 cases of primary epithelial ovarian cancer (EOC) and 6 cases of normal ovarian tissues were collected, and the levels of protein expression of BRCA1, BRCA2, RAD51, and FANCD2 were detected by immunohistochemistry. The expression of the above four proteins in the EOC tissues and the correlation between the proteins in the cancer genome atlas (TCGA) database through GEPIA. Ualcan analyzed the relationship between the expression of the four proteins and the clinicopathological characteristics of EOC in the TCGA database. Results: Immunohistochemical assays revealed that BRCA2, FANCD2 and RAD51 were highly expressed in EOC specimens rather than in normal tissues (all P<0.05). According to the analyses of TCGA database by GEPIA, the mRNA expression of BRCA1, BRCA2, RAD51 and FANCD2 increased in EOC tissues. The expression levels of 4 proteins have a significant positive correlation between each other. According to the results of TCGA database by Ualcan analysis, the mRNA expression of BRCA1 was significantly higher in patients over 41 years of age; expression of these four genes were higher in tumors above grade 2 and the mRNA expression of RAD51 in grade 3 tumors was significantly higher than that in grade 2 tumors; the mRNA expression of FANCD2 in African American was significantly higher than that in Caucasian; the mRNA expression of BRCA1, RAD51, and FANCD2 in TP53mutant tumors was significantly higher than their expression in nonmutant tumors. Conclusion: The expression of BRCA2, FANCD2 and RAD51 was significantly increased in tumor tissues of EOC, and may potentially be candidate biomarkers for diagnosis and treatment of ovarian cancer.

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收稿日期: 2021-01-28

基金资助:国家自然科学基金面上项目（81672582，31771521）；国家自然科学基金青年项目（81402145）；江苏省重点研发（社会发展）项目（BE2016718）

通讯作者: 刘晗青（通讯作者），教授，硕士生导师，E-mail：hanqing@ujs.edu.cn；屠志刚（通讯作者），研究员，博士生导师，E-mail：zhigangtu@ujs.edu.cn

作者简介: 刘兰兰(1993—)，女，硕士研究生；

引用本文:

刘兰兰，王志新，袁思锐，石春燕，卢子文，胡兴，刘晗青，屠志刚. BRCA1、BRCA2、RAD51和FANCD2在上皮性卵巢癌中的表达及其与临床病理特征的关系[J]. 江苏大学学报:医学版, 2022, 32(02): 113-117,123. LIU Lanlan， WANG Zhixin， YUAN Sirui， SHI Chunyan， LU Ziwen， HU Xing， LIU Hanqing， TU Zhigang. Expression of BRCA1, BRCA2, RAD51 and FANCD2 in ovarian cancer tissues and correlation with clinicopathological characteristics. Journal of Jiangsu University(Medicine Edition), 2022, 32(02): 113-117,123.

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http://zzs.ujs.edu.cn/xbyxb/CN/ 或 http://zzs.ujs.edu.cn/xbyxb/CN/Y2022/V32/I02/113

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