肿瘤-睾丸抗原联蛋白α2在肝细胞癌中的表达及临床意义的多组学研究  

Multi-omics study on the expression of cancer-testis antigen catenin alpha 2 in hepatocellular carcinoma and its clinical significance

作　　者：张娟 陈茂培 董良庆 林友培 潘教孟 宋国贺 阿晔岭 张舒 高强 任正刚 ZHAGN Juan;CHEN Mao-pei;DONG Liang-qing;LIN You-pei;PAN Jiao-meng;SONG Guo-he;A Ye-ling;ZHANG Shu;GAO Qiang;REN Zheng-gang(Liver Cancer Institute,Key Laboratory of Ministry of Education of Carcinogenesis and Cancer Invasion,Fudan University,Zhongshan Hospital,Shanghai 200032,China)

机构地区：[1]复旦大学附属中山医院肝癌研究所,复旦大学癌变与侵袭原理教育部重点实验室,上海200030

出　　处：《中国临床医学》2021年第1期27-35,共9页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金(91859105,81802360,81961128025);上海市科学技术委员会基础研究项目(17JC1402200).

摘　　要：目的:借助多组学策略观察肿瘤-睾丸抗原联蛋白α2(catenin alpha 2,CTNNA2)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达情况,探讨其在HCC免疫治疗中的潜在价值及临床意义。方法:分析CTNNA2在159例乙型肝炎病毒(HBV)相关HCC和配对癌旁组织中,mRNA和蛋白的表达水平及差异,并进一步采用免疫蛋白质组学检测与主要组织相容性复合体Ⅰ(major histocompatibility complex,MHC-Ⅰ)结合的CTNNA2抗原多肽。采用反转录多聚酶链反应(RT-PCR)验证33对HCC和癌旁组织cDNA及12种HCC细胞株中CTNNA2的表达情况,同时探讨CTNNA2参与肿瘤调控的可能机制。结果:转录组测序技术(RNA sequencing,RNA-Seq)定量转录组学和串联质谱标签(tandem mass tag,TMT)定量蛋白质组学结果均提示,CTNNA2在HCC组织中显著高表达。RNA-seq结果提示,CTNNA2表达阳性率为80.5%,较癌旁表达高11.24倍(P<0.001),TMT定量蛋白组学显示,HCC癌组织中CTNNA2表达阳性率为54.7%,较癌旁表达高2.66倍(P<0.001)。经免疫蛋白质组学检测,本研究发现30种可能与MHC-Ⅰ结合的CTNNA2抗原多肽。结论:多组学研究结果提示,CTNNA2在HCC中高表达,CTNNA2可能是新的肝癌疫苗靶分子。Objective:To observe the expression of cancer-testis antigen(CTA)catenin alpha 2(CTNNA2)in hepatocellular carcinoma(HCC)based on multi-omics data and investigate its potential clinical significance in HCC immunotherapy.Methods:The mRNA and protein levels of CTNNA2 were analyzed in 159 paired hepatitis B virus(HBV)related HCC and non-tumor liver tissues.Further,the immunoproteomics was used to detect the CTNNA2 antigen polypeptide binding with major histocompatibility complex(MHC-Ⅰ).The expression of CTNNA2 in 33 paired tumor and non-tumor liver tissues and 12 HCC cell lines was verified by reverse transcription polypolymerase chain reaction(RT-PCR).The potential mechanism of CTNNA2 in HCC was also explored.Results:RNA sequencing(RNA-Seq)quantitative transcriptomics and tandem mass tag(TMT)-based quantitative proteomics data indicated CTNNA2 was significantly highly expressed in HCC tissues.RNA-Seq analysis suggested that CTNNA2 mRNA expressed in 80.5%HCC,11.24 times higher than that in the non-tumor liver tissues(P<0.001).TMT-based quantitative proteomics analysis showed that the CTNNA2 protein were expressed in 54.7%of HCC,2.66 times higher than that in the non-tumor liver tissues.Immunoproteomics detected 30 kinds of CTNNA2 antigen polypeptides which could bind to MHC-Ⅰ(P<0.001).Conclusions:Multi-omics analysis suggests that CTNNA2 is significantly upregulated in HCC and may be a new target of tumor vaccination.

关 键 词：肝细胞癌 肿瘤睾丸抗原 联蛋白α2 转录组学 蛋白组学 免疫蛋白组学 

分 类 号：R735.7[医药卫生—肿瘤]