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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 |
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
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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
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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。 |
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 |
DOI:10.12025/j.issn.1008-6358.2021.20202336 |
分类号:R735.7 |
基金项目: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). |
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Multi-omics study on the expression of cancer-testis antigen catenin alpha 2 in hepatocellular carcinoma and its clinical significance |
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
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Liver Cancer Institute, Key Laboratory of Ministry of Education of Carcinogenesis and Cancer Invasion, Fudan University, Zhongshan Hospital, Shanghai 200032, China
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Abstract: |
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. |
Key words: hepatocellular carcinoma tumor testis antigen catenin alpha 2 transcriptomics proteomics immunoproteomics |