近年来,随着越来越多的肺癌患者接受免疫治疗剂的治疗,与以前相比,它们的生存期延长了。众所周知,BTK(布鲁顿酪氨酸激酶)主要存在于造血系统的细胞中。然而,关于BTK在肺腺癌(LUAD)患者中的表达及其对免疫微环境的影响的文献明显缺乏。因此,这项研究的主要目的是分析BTK在肺腺癌中的表达如何影响其进展,连同其预后意义,通过利用生物信息学在线资源和公开可用的数据库。从癌症基因组图谱(TCGA)数据库收集关于肺腺癌患者的测序结果和临床记录的数据。根据BKT的表达水平,TCGA将肺腺癌患者分为BTK高表达和低表达组。我们调查了BKT对临床病理,基因组,肺腺癌患者的免疫学特征。我们使用两个关键资源分析了肿瘤和正常组织中的BTKmRNA表达:肿瘤免疫评估资源2.0(TIMER2.0)和基因表达谱交互式分析2(GEPIA2)。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,我们通过人蛋白图谱(HPA)评估BTK蛋白表达。我们试图使用在线工具GEPIA2阐明BTK在TCGA中的临床预后意义。此外,为了阐明与BTK相关的生物学作用和途径,我们对这些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的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。使用TIMER和CIBERSORT,探讨了与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,使用TCGA数据库通过R语言分析分析TMB组及高低组BTK表达与免疫浸润和免疫检查点之间的关系.BTK的表达为患者的预后提供了一些提示。BTK的高表达参与免疫应答调控信号通路,白细胞介导的免疫,白细胞细胞间粘附,移植排斥,和补充。对GEPIA2数据库的分析表明,BTK与FGD2,SASH3,NCKAP1L基因共表达,CD53、ARHGAP30和LPXN。上述基因的表达增加导致CD8+T细胞的比例增加,记忆CD4+T细胞,B细胞,巨噬细胞,和树突状细胞,Treg细胞和TH2细胞比例降低。此外,我们的研究表明,各种关键免疫检查点之间存在很强的正相关(例如,PDCD1,CD274,PDCD1LG2,CTLA4,HAVCR2,LAG3,TIGIT,和SIGLEC15)和BTK表达。总之,BTK在肺腺癌中的表达增加与肺癌患者的生存期延长密切相关。此外,在BTK高表达组中分类的基因在免疫相关途径中表现出显著的富集,提示对肿瘤微环境的潜在影响。我们研究了BTK作为肿瘤抑制基因在预测患者生存期延长方面的潜力。此外,我们进一步探讨了BTK通过影响肿瘤免疫浸润的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。
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.