| 肖淑秀,林志远,宋正清,姚梦菲,卢莉莉.CD39的临床意义及其与肝癌浸润T细胞耗竭的相关性分析[J].,2023,(10):1815-1821 |
| CD39的临床意义及其与肝癌浸润T细胞耗竭的相关性分析 |
| Analysis of CD39 Clinical Significance Hepatocellular Carcinoma and Its Correlation with T Cell Exhaustion |
| 投稿时间：2023-01-23 修订日期：2023-02-17 |
| DOI：10.13241/j.cnki.pmb.2023.10.003 |
| 中文关键词: 肝癌 CD39 CD8+T细胞耗竭 生信分析 |
| 英文关键词: Hepatocellular carcinoma CD39 CD8+T cell exhaustion Bioinformatics analysis |
| 基金项目:上海市科委"科技创新行动计划"扬帆计划项目（20YF1406100）；上海市卫健委科研计划项目（20204Y0229） |
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| 中文摘要: |
| 摘要 目的：探索CD39分子（编码基因ENTPD1）在原发性肝细胞肝癌（Hepatocellular carcinoma, HCC）中的表达、临床意义及其与HCC中免疫浸润和T细胞耗竭的相关性。方法：TIMER、GEPIA、Kaplan-Meier Plotter、TCGA等数据库分析CD39在肝癌中的差异性表达、与免疫浸润的关系、相关基因的表达及其与肝癌患者预后的关系。免疫荧光染色、细胞测序和流式检测验证临床HCC患者的癌及癌旁组织中CD39的差异性表达及其和CD8+T细胞耗竭特性的相关性。结果：（1）生物信息学分析结果显示：CD39在多种肿瘤组织中表达上调（包括HCC）（P＜0.05）；且其表达水平与HCC的临床预后等显著相关（P＜0.05）；与CD39低表达组相比，HCC中CD39高表达组患者无复发生存期（relapse-free survival, RFS）（P=0.025）和无进展生存期（progression-free survival, PFS）（P=0.026）较短；CD39与HCC肿瘤微环境中CD8+T、CD4+T、巨噬细胞等免疫细胞浸润水平均有明显正相关。（2）临床HCC样本验证：免疫荧光和流式结果显示CD39在癌组织中的表达水平高于癌旁正常组织，与耗竭相关分子LAYN、TIM3、CTLA4等共表达，且在耗竭CD8+T细胞中表达比例显著高于非耗竭细胞。结论：CD39在HCC肿瘤组织及浸润的CD8+T细胞中高表达，与HCC的RFS、PFS、免疫细胞浸润等紧密相关，且参与CD8+T细胞耗竭。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the expression and clinical significance of CD39 (encoding gene ENTPD1) in Hepatocellular carcinoma and its correlation with immune infiltration and T cell exhaustion in HCC tumor microenvironment. Methods: The mRNA expression of CD39 in HCC and its correlation with immune infiltration, correlated genes and prognosis of HCC were assessed by TIMER, GEPIA, Kaplan-Meier Plotter databases. The differential expression of CD39 in HCC specimens and its relationship with CD8+T cell exhaustion were further verified by immunofluorescence, cell sequence and flow cytometry. Results: (1) Bioinformatics data showed that CD39 expression was upregulated in a variety of tumor tissues (including HCC) (P＜0.05). And its expression level was significantly related to the clinical prognosis of HCC. HCC patients with high expression of CD39 had shorter relapse-free survival(P=0.025) and progression-free survival (P=0.026) than those low expression group. The results of immune infiltration analysis indicated that CD39 expression level was positively correlated with the infiltration levels of CD8+T, CD4+T, and macrophages in HCC tumor microenvironment. (2) Immunofluorescence and flow cytometry results revealed that transcriptional and protein levels of CD39 were both higher in HCC tumors than adjacent tissues. And, CD39 was co-expressed with LAYN, TIM3 and CTLA4, and the expression level of CD39 in exhausted CD8+T cells was significantly higher than that in non-exhausted cells. Conclusion: CD39 is highly expressed in HCC tumor tissues and CD8+T cells, which is closely related to RFS, PFS and immune cell infiltration of HCC. And, CD39 participates in CD8+T cell exhaustion process, which may be a potential immunotherapy target for HCC patients. |
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