慢性阻塞性肺疾病是肺癌中最常见的类型。尽管在慢性阻塞性肺病的免疫机制和相关分子的研究方面已经有所突破，但这些分子在免疫微环境中的具体调节机制仍不清楚。此外，我们还尚未了解到调控基因或RNA对慢性阻塞性肺病的转移和生存时间的影响。为填补这些知识空白，我们收集了大量的数据，包括1018个样本的17226个基因表达谱、461个样本的370640个甲基化位点和513个样本的 248个miRNA。我们的目标是探索与慢性阻塞性肺病发展相关的基因、miRNA和甲基化位点。通过利用miRNA和甲基化位点的调控功能，我们确定了靶基因和调节基因。通过使用LASSO和生存分析，我们确定了22个在慢性阻塞性肺病免疫调控机制中起关键作用的基因。值得注意的是，这22个基因的表达水平在预测慢性阻塞性肺病患者存活时间方面具有显著的判别力。此外，我们的深度学习模型利用这些基因的表达水平准确预测了慢性阻塞性肺病患者的远处转移。进一步的通路富集分析揭示了这22个基因在与慢性阻塞性肺病发展密切相关的通路中显著富集。通过免疫浸润分析，我们观察到T细胞CD4记忆静置、单核细胞和巨噬细胞M2是慢性阻塞性肺病免疫微环境中最丰富的三种细胞类型。这些细胞在肿瘤生长、侵袭和转移中起着重要作用。单细胞数据分析进一步验证了这些基因的功能重要性，表明它们不仅参与免疫细胞，而且在上皮细胞中也有显著差异表达。总的来说，本研究通过确定与慢性阻塞性肺病发展相关的关键基因，揭示了慢性阻塞性肺病免疫微环境的调节机制。研究结果为潜在的预后标志物和治疗靶点提供了见解。 版权© 2023 Elsevier Ltd. 出版。

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Despite previous research on immune mechanisms and related molecules in LUAD, the specific regulatory mechanisms of these molecules in the immune microenvironment remain unclear. Furthermore, the impact of regulatory genes or RNA on LUAD metastasis and survival time is yet to be understood. To address these gaps, we collected a substantial amount of data, including 17,226 gene expression profiles from 1,018 samples, 370,640 methylation sites from 461 samples, and 248 miRNAs from 513 samples. Our aim was to explore the genes, miRNAs, and methylation sites associated with LUAD progression. Leveraging the regulatory functions of miRNAs and methylation sites, we identified target and regulated genes. Through the utilization of LASSO and survival analysis, we pinpointed 22 key genes that play pivotal roles in the immune regulatory mechanism of LUAD. Notably, the expression levels of these 22 genes demonstrated significant discriminatory power in predicting LUAD patient survival time. Additionally, our deep learning model accurately predicted distant metastasis in LUAD patients using the expression levels of these genes. Further pathway enrichment analysis revealed that these 22 genes are significantly enriched in pathways closely linked to LUAD progression. Through Immune Infiltration Assay, we observed that T cell CD4 memory resting, monocytes, and macrophages.M2 were the three most abundant cell types in the immune microenvironment of LUAD. These cells are known to play crucial roles in tumor growth, invasion, and metastasis. Single-cell data analysis further validated the functional significance of these genes, indicating their involvement not only in immune cells but also in epithelial cells, showcasing significant differential expression. Overall, this study sheds light on the regulatory mechanisms underlying the immune microenvironment of LUAD by identifying key genes associated with LUAD progression. The findings provide insights into potential prognostic markers and therapeutic targets.Copyright © 2023. Published by Elsevier Ltd.