基于生物信息学的CD39对肺腺癌免疫微环境及其免疫治疗的影响分析

目的 采用生物信息学方法探讨CD39基因在肺腺癌组织中的表达情况，并分析CD39与肺腺癌免疫微环境及免疫治疗响应的关系。方法 通过The Cancer Genome Atlas （TCGA）数据库分析CD39在肺腺癌组织和正常肺组织中的表达差异。采用基因集富集分析（GSEA）研究CD39可能富集的免疫相关通路；通过肿瘤免疫数据库（TIMER）分析肺腺癌患者中CD39基因表达情况与肿瘤微环境免疫细胞浸润的关系；同时分析CD39和其他免疫检查点基因PD-1、PD-L1、CTLA-4、IDO1的相关性，采用药物敏感性基因组学数据库（GDSC）和肿瘤免疫功能障碍和排斥（TIDE）数据库，预测CD39基因表达与化疗药物敏感性以及免疫治疗的响应。结果 CD39在肺腺癌组织中的表达低于在正常组织中的表达，CD39富集了免疫相关通路如炎症反应、干扰素α反应、干扰素γ反应。TIMER数据库均显示在肺腺癌组织中，CD39的表达与B细胞、CD8⁺T细胞、CD4⁺T细胞、巨噬细胞、中性粒细胞以及树突状细胞呈正相关性。同时CD39与其他的免疫检查点PD-1、PD-L1、CTLA-4、IDO1均呈一定的正相关性，化疗敏感性显示在肺腺癌组织中，对于博来霉素、顺铂、多西他赛、长春花碱等化疗药物，高表达CD39组对其敏感。但对于免疫治疗，其响应率却低于CD39低表达组。结论 CD39在肺腺癌组织中低表达，能激活免疫相关通路，对免疫治疗响应率高，可作为肺腺癌新型分子标志物。

Research on effect for immunotherapy of CD39 and its role on immunemicroenvironment and immunotherapy in lung adenocarcinoma based on bioinformatics

Objective To investigate the relationship between CD39 in lung adenocarcinomaand the prediction the efficacy of immunotherapy. Methods The gap for the expression of CD39 between lung adenocarcinoma and normal tissues were completed through The Cancer Genome Atlas (TCGA) database. With the help of Gene Set Enrichment Analysis (GSEA), CD39 involved immune-related pathways were exploited. What more, the relationship between CD39 expression in lung adenocarcinoma and immune cells infiltration in the tumor microenvironment was accomplished by using the TIMER databases as well as other immunerelated molecules such as PD-1, PD-L1, CTLA-4, IDO-1. According to the GDSC database, the relationship between CD39 expression and chemotherapy drug sensitivity by taking IC₅₀ value as the indicator was found. The TIDE algorithm was also exploited to calculate response for the immunotherapy. Results CD39 was lower in lung adenocarcinoma when compared to normal tissue. According to GSEA results, CD39 could activate immune-related pathways such as the inflammatory response, interferon alpha response, interferon alpha gamma response. As for immune microenvironment in lung adenocarcinoma, the expression level of CD39 was positively correlated with the infiltration level of B-cells, CD8⁺ T-cells, CD4⁺ T-cells, macrophage, neutrophils and dendritic cells according to the TIMER database. The same phenomenon was also occurred with other immune checkpoints such as PD-1, PD-L1, CTLA-4, IDO1. Chemotherapy sensitivity indicated that in lung adenocarcinoma, high level of CD39 expression could be sensitive to chemotherapy drugs such as bleomycin, cisplatin, docetaxel, vinblastine. But for immunotherapy, patients with low CD39 expression could get a good result. Conclusion CD39 is low expressed in lung adenocarcinoma which is beneficial for immunotherapy and participates in immune related pathways. It can be used as a novel molecular marker for lung adenocarcinoma.