基于生物信息学分析探讨CD59在肺癌中的表达及其临床意义  

Analysis of Expression and Clinical Significance of CD59 in Lung Cancer Based on Bioinformatics Databases

作　　者：王卫东 董婧珂 龚永生[2] 孙慧[3] 王洁[4] 金艳霞 WANG Wei-dong;DONG Jing-ke;GONG Yong-sheng;SUN Hui;WANG Jie;JIN Yan-xia(College of Life Sciences,Hubei Key Laboratory of Edible Wild Plants Conservation and Utilization,Hubei Engineering Research Center of Special Wild Vegetables Breeding and Comprehensive Utilization Technology,National Demonstration Center for Experimental Biology Education,Hubei Normal University,Huangshi 435002,Hubei,China;Suzhou Municipal Hospital,the Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215008,Jiangsu,China;College of Life Sciences,Wuhan University,Wuhan 430072,Hubei,China;Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei,China)

机构地区：[1]湖北师范大学生命科学学院,食用野生植物保育与利用湖北省重点实验室,特色野菜良种繁育与综合利用湖北省工程技术研究中心,生物学国家级实验教学示范中心,中国湖北黄石435002 [2]南京医科大学附属苏州医院,中国江苏苏州215008 [3]武汉大学生命科学学院,中国湖北武汉430072 [4]华中科技大学同济医院,中国湖北武汉430030

出　　处：《生命科学研究》2022年第4期361-369,376,共10页Life Science Research

基　　金：国家自然科学基金青年项目(32000908);湖北省科技厅自然科学基金项目(2020CFB417);食用野生植物保育与利用湖北省重点实验室开放课题基金项目(EWPL201801);湖北师范大学2018年引进人才科研启动基金项目(HS2019RC008)。

摘　　要：CD59为含128个氨基酸的糖基磷脂酰肌醇锚定的糖蛋白,是膜结合性补体调节蛋白的重要成员,在血液和多种组织中表达。本研究通过转录组测序数据分析发现,CD59在早期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的外周血白细胞中表达下调,在此基础上,利用Oncomine、GEPIA、UniProt、COMSIC、SWISS-MODEL、STRING和Kaplan-Meier Plotter等数据库探讨了CD59在肺癌中的表达、蛋白质结构变化及其与患者生存之间的关系,并利用免疫印迹法(Western-blot)分析了CD59在早期肺癌组织和血清中的水平。Oncomine和GEPIA数据库分析发现,CD59的m RNA在肺癌组织中表达下降;Western-blot实验证实,CD59蛋白在早期肺癌组织和血清中的水平也下降。COSMIC数据库分析发现,肺癌患者中的CD59蛋白有3个氨基酸位点(即8、87和128位)存在突变,其中第8和128位点的突变属于同义突变,而第87位的氨基酸由酪氨酸(Y)突变为苯丙氨酸(F);进一步的SWISS-MODEL同源模建结果显示,第87位酪氨酸仅与第53位异亮氨酸(I)有氢键作用,突变成苯丙氨酸后,其与53位异亮氨酸之间的氢键并未发生变化。蛋白质相互作用网络分析发现,CD59蛋白与CD55、C9、C3AR1、C8A、C8B、INS、PLAUR、CD47、ITGAM和CEACAM8有相互作用。Kaplan-Meier Plotter数据库分析发现,CD59低表达的肺癌患者生存时间更短。本研究通过生物信息学分析CD59在肺癌中的表达情况及临床意义,为进一步探索CD59参与肺癌发生机制和预后判断提供了参考依据。CD59 is a glycosylphosphatidylinositol-anchored glycoprotein that consists of 128 amino acids,and is an important member of membrane-bound complement regulatory proteins,which is expressed in blood and a variety of tissues.In this study,transcriptome sequencing data analysis found that the CD59 expression was down-regulated in leukocytes of peripheral blood in patients with early non-small cell lung cancer(NSCLC).On this basis,the protein structure and expression change of CD59 in lung cancer,and the relationship between CD59 expression and the survival of lung cancer patients were analyzed by using databases of Oncomine,GEPIA,UniProt,COMSIC,SWISS-MODEL,STRING and Kaplan-Meier Plotter.Further,the CD59 protein expression levels in the tissues and sera of early lung cancer were analyzed by Western-blot.Oncomine and GEPIA database analysis showed decreased mRNA expression of CD59 in lung cancer tissues,and Western-blot also showed decreased CD59 protein expression levels in the tissues and sera of early lung cancer.Based on COSMIC database analysis,there were three mutated sites(the 8th,87th,and 128th amino acids)in the CD59 protein of lung cancer patients.The mutated sites at both 8th and128th amino acids were synonymous mutations,while the amino acid site at tyrosine(Y)87 was mutated into phenylalanine(F).Meanwhile,the CD59 protein structure was constructed by using the SWISS-MODEL.It was found that tyrosine 87 had hydrogen bonding only with isoleucine(I)53,and the hydrogen bonding force did not change between phenylalanine 87 and isoleucine 53 in the CD59 mutant when analyzed by SPDBV software,therefore this mutation may not change the protein structure.The protein-protein interaction network analysis showed that CD59 protein was interacted with ten proteins including CD55,C9,C3AR1,C8A,C8B,INS,PLAUR,CD47,ITGAM and CEACAM8.Kaplan-Meier Plotter database analysis revealed that the patients with lower CD59 expression had a shorter survival time.The analysis of CD59 involvement in lung cancer in this study may provide

关 键 词：肺癌 CD59蛋白 表达水平 生存分析 生物信息学 数据库 

分 类 号：Q811.4[生物学—生物工程] R734.2[医药卫生—肿瘤]