近年来，随着越来越多的肺癌患者接受免疫治疗药物的治疗，他们的生存期较以前有所延长。众所周知，BTK（布鲁顿酪氨酸激酶）主要存在于造血系统细胞中。然而，关于肺腺癌（LUAD）患者中BTK表达及其对免疫微环境影响的文献明显缺乏。因此，本研究的主要目标是通过利用生物信息学在线资源和公开数据库来分析肺腺癌中 BTK 表达如何影响其进展及其预后意义。肺腺癌患者的测序结果和临床记录数据来自癌症基因组图谱（TCGA）数据库。 TCGA根据BKT的表达水平将肺腺癌患者分为BTK高表达组和低表达组。我们研究了 BKT 对肺腺癌患者的临床病理学、基因组和免疫学特征的影响。我们使用两个关键资源分析了肿瘤和正常组织中的 BTK mRNA 表达：肿瘤免疫估计资源 2.0 (TIMER 2.0) 和基因表达谱交互分析 2 (GEPIA 2)。我们使用 GEPIA2 分析了患者的预后，并使用单变量和多变量分析验证了结果。此外，我们通过人类蛋白质图谱 (HPA) 评估了 BTK 蛋白表达。我们试图使用在线工具 GEPIA 2 阐明 TCGA 中 BTK 的临床预后意义。此外，为了阐明与 BTK 相关的生物学作用和途径，我们对信息进行了基因组富集分析。为了预测TCGA数据库中诊断的肺腺癌患者免疫微环境中各种免疫细胞浸润的比例，我们使用TIMER在线工具进行了分析。利用TIMER和CIBERSORT，探索与BTK共表达的基因与相应的肿瘤浸润免疫细胞之间的相关性；最后利用TCGA数据库通过R语言分析TMB组及高、低组中BTK表达与免疫浸润、免疫检查点的关系。 BTK的表达为患者的预后提供了一些提示。 BTK的高表达参与免疫反应调节信号通路、白细胞介导的免疫、白细胞细胞间粘附、移植排斥和补体。 GEPIA 2数据库分析表明BTK与FGD2、SASH3、NCKAP1L、CD53、ARHGAP30和LPXN基因共表达。上述基因表达增加导致CD8  T细胞、记忆CD4  T细胞、B细胞、巨噬细胞和树突状细胞比例增加，Treg细胞和TH2细胞比例减少。此外，我们的研究揭示了各种关键免疫检查点（例如 PDCD1、CD274、PDCD1LG2、CTLA4、HAVCR2、LAG3、TIGIT 和 SIGLEC15）与 BTK 表达之间存在很强的正相关性。总之，肺腺癌中BTK表达增加与肺癌患者的生存期延长密切相关。此外，BTK 高表达组下的基因在免疫相关通路中表现出显着富集，表明对肿瘤微环境具有潜在影响。我们研究了 BTK 作为肿瘤抑制基因在预测延长患者生存期方面的潜力。此外，我们进一步探讨了BTK通过影响肿瘤免疫浸润微环境进一步影响患者免疫治疗反应的可能性，但相关机制仍有待进一步研究。© King Abdulaziz City for Science and Technology 2024。 Springer Nature 或其许可方（例如协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议拥有本文的专有权；作者对本文已接受的手稿版本的自行存档仅受此类出版协议和适用法律的条款的约束。

In recent years, as more and more lung-cancer patients have been treated with immunotherapeutic agents, their survival has been prolonged compared to before. It is well known that BTK (Bruton's tyrosine kinase) is predominantly found in cells of the hematopoietic system. However, there is a distinct lack of literature on BTK expression in lung adenocarcinoma (LUAD) patients and its effect on the immune microenvironment. Consequently, the main goal of this investigation was to analyze how BTK expression in lung adenocarcinoma affects its progression, along with its prognostic significance, through the utilization of bioinformatics online resources and publicly available databases. Data on the sequencing results and clinical records of lung adenocarcinoma patients were gathered from The Cancer Genome Atlas (TCGA) database. Based on the expression level of BKT, TCGA categorized lung adenocarcinoma patients into BTK high-expression and low-expression groups. We investigated the effects of BKT on clinicopathologic, genomic, and immunologic characteristics of lung adenocarcinoma patients. We analyzed BTK mRNA expression in tumors and normal tissues using two key resources: Tumor Immuno Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). We analyzed the prognosis of the patients using GEPIA2 and validated the results using univariate and multivariate analyses. In addition, we assessed BTK protein expression by Human Protein Atlas (HPA). We sought to elucidate the clinical prognostic significance of BTK in The TCGA using the online tool GEPIA 2. Furthermore, to clarify the biologic roles and pathways linked to BTK, we conducted a genomic enrichment analysis of the information. To predict the proportion of various immune cell infiltrations in the immune microenvironment of lung adenocarcinoma patients diagnosed in the TCGA database, we performed an analysis using the TIMER online tool. Using TIMER and CIBERSORT, the correlation between genes co-expressed with BTK and the corresponding tumor-infiltrating immune cells was explored; finally, the relationship between BTK expression and immune infiltration and immune checkpoints in the TMB group and the high and low groups was analyzed by R language analysis using the TCGA database. The expression of BTK provides some hints about the prognosis of the patients. The high expression of BTK is involved in immune response regulation signaling pathways, leukocyte-mediated immunity, leukocyte intercellular adhesion, graft rejection, and complement. Analysis of the GEPIA 2 database showed that BTK was co-expressed with the genes FGD2, SASH3, NCKAP1L, CD53, ARHGAP30 and LPXN. Increased expression of the above-mentioned genes resulted in increased proportions of CD8 + T cells, memory CD4 + T cells, B cells, macrophages, and dendritic cells, and decreased proportions of Treg cells and TH2 cells. In addition, our study revealed a strong positive correlation between various key immune checkpoints (e.g., PDCD1, CD274, PDCD1LG2, CTLA4, HAVCR2, LAG3, TIGIT, and SIGLEC15) and BTK expression. In conclusion, increased BTK expression in lung adenocarcinoma is closely associated with prolonged survival of lung-cancer patients. Moreover, the genes classified under the BTK high-expression group exhibit significant enrichment in immune-related pathways, suggesting a potential impact on the tumor microenvironment. We investigated the potential of BTK as a tumor suppressor gene in predicting prolonged patient survival. In addition, we further investigated the possibility that BTK further affects the immunotherapeutic response of patients by influencing the microenvironment of tumor immune infiltration, but the relevant mechanisms remain to be further studied.© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.