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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

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

    摘要
  • 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。

     

    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.

     

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