目的 采用生物信息學(xué)方法探討CD39基因在肺腺癌組織中的表達(dá)情況，并分析CD39與肺腺癌免疫微環(huán)境及免疫治療響應(yīng)的關(guān)系。方法 通過(guò)The Cancer Genome Atlas （TCGA）數(shù)據(jù)庫(kù)分析CD39在肺腺癌組織和正常肺組織中的表達(dá)差異。采用基因集富集分析（GSEA）研究CD39可能富集的免疫相關(guān)通路；通過(guò)腫瘤免疫數(shù)據(jù)庫(kù)（TIMER）分析肺腺癌患者中CD39基因表達(dá)情況與腫瘤微環(huán)境免疫細(xì)胞浸潤(rùn)的關(guān)系；同時(shí)分析CD39和其他免疫檢查點(diǎn)基因PD-1、PD-L1、CTLA-4、IDO1的相關(guān)性，采用藥物敏感性基因組學(xué)數(shù)據(jù)庫(kù)（GDSC）和腫瘤免疫功能障礙和排斥（TIDE）數(shù)據(jù)庫(kù)，預(yù)測(cè)CD39基因表達(dá)與化療藥物敏感性以及免疫治療的響應(yīng)。結(jié)果 CD39在肺腺癌組織中的表達(dá)低于在正常組織中的表達(dá)，CD39富集了免疫相關(guān)通路如炎癥反應(yīng)、干擾素α反應(yīng)、干擾素γ反應(yīng)。TIMER數(shù)據(jù)庫(kù)均顯示在肺腺癌組織中，CD39的表達(dá)與B細(xì)胞、CD8⁺T細(xì)胞、CD4⁺T細(xì)胞、巨噬細(xì)胞、中性粒細(xì)胞以及樹(shù)突狀細(xì)胞呈正相關(guān)性。同時(shí)CD39與其他的免疫檢查點(diǎn)PD-1、PD-L1、CTLA-4、IDO1均呈一定的正相關(guān)性，化療敏感性顯示在肺腺癌組織中，對(duì)于博來(lái)霉素、順鉑、多西他賽、長(zhǎng)春花堿等化療藥物，高表達(dá)CD39組對(duì)其敏感。但對(duì)于免疫治療，其響應(yīng)率卻低于CD39低表達(dá)組。結(jié)論 CD39在肺腺癌組織中低表達(dá)，能激活免疫相關(guān)通路，對(duì)免疫治療響應(yīng)率高，可作為肺腺癌新型分子標(biāo)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(guó)家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2021YFC2401103）