目的 采用生物信息學方法探討CD39基因在肺腺癌組織中的表達情況，并分析CD39與肺腺癌免疫微環(huán)境及免疫治療響應的關系。方法 通過The Cancer Genome Atlas （TCGA）數(shù)據(jù)庫分析CD39在肺腺癌組織和正常肺組織中的表達差異。采用基因集富集分析（GSEA）研究CD39可能富集的免疫相關通路；通過腫瘤免疫數(shù)據(jù)庫（TIMER）分析肺腺癌患者中CD39基因表達情況與腫瘤微環(huán)境免疫細胞浸潤的關系；同時分析CD39和其他免疫檢查點基因PD-1、PD-L1、CTLA-4、IDO1的相關性，采用藥物敏感性基因組學數(shù)據(jù)庫（GDSC）和腫瘤免疫功能障礙和排斥（TIDE）數(shù)據(jù)庫，預測CD39基因表達與化療藥物敏感性以及免疫治療的響應。結果 CD39在肺腺癌組織中的表達低于在正常組織中的表達，CD39富集了免疫相關通路如炎癥反應、干擾素α反應、干擾素γ反應。TIMER數(shù)據(jù)庫均顯示在肺腺癌組織中，CD39的表達與B細胞、CD8⁺T細胞、CD4⁺T細胞、巨噬細胞、中性粒細胞以及樹突狀細胞呈正相關性。同時CD39與其他的免疫檢查點PD-1、PD-L1、CTLA-4、IDO1均呈一定的正相關性，化療敏感性顯示在肺腺癌組織中，對于博來霉素、順鉑、多西他賽、長春花堿等化療藥物，高表達CD39組對其敏感。但對于免疫治療，其響應率卻低于CD39低表達組。結論 CD39在肺腺癌組織中低表達，能激活免疫相關通路，對免疫治療響應率高，可作為肺腺癌新型分子標志物。

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.

R979.1

國家重點研發(fā)計劃項目（2021YFC2401103）