Cardiothoracic Surgery, The First People's Hospital of Kunming City & Ganmei Affiliated Hospital of Kunming Medical University, Kunming, 650000 Yunnan Province, China.
Department of Thoracic Surgery, Kunming Yan'an Hospital Affiliated to Kunming Medical University, Kunming, 650000 Yunnan Province, China.
Mediators Inflamm. 2022 Sep 22;2022:1878766. doi: 10.1155/2022/1878766. eCollection 2022.
The purpose of this study was to uncover potential diagnostic indicators of pulmonary arterial hypertension (PAH), evaluate the function of immune cells in the pathogenesis of the disease, and find innovative treatment targets and medicines with the potential to enhance prognosis. Gene Expression Omnibus was utilized to acquire the PAH datasets. We recognized differentially expressed genes (DEGs) and investigated their functions utilizing R software. Weighted gene coexpression network analysis, least absolute shrinkage and selection operators, and support vector machines were used to identify biomarkers. The extent of immune cell infiltration in the normal and PAH tissues was determined using CIBERSORT. Additionally, the association between diagnostic markers and immune cells was analyzed. In this study, 258DEGs were used to analyze the disease ontology. Most DEGs were linked with atherosclerosis, arteriosclerotic cardiovascular disease, and lung disease, including obstructive lung disease. Gene set enrichment analysis revealed that compared to normal samples, results from PAH patients were mostly associated with ECM-receptor interaction, arrhythmogenic right ventricular cardiomyopathy, the Wnt signaling pathway, and focal adhesion. FAM171B was identified as a biomarker for PAH (area under the curve = 0.873). The mechanism underlying PAH may be mediated by nave CD4 T cells, resting memory CD4 T cells, resting NK cells, monocytes, activated dendritic cells, resting mast cells, and neutrophils, according to an investigation of immune cell infiltration. FAM171B expression was also associated with resting mast cells, monocytes, and CD8 T cells. The results suggest that PAH may be closely related to FAM171B with high diagnostic performance and associated with immune cell infiltration, suggesting that FAM171B may promote the progression of PAH by stimulating immune infiltration and immune response. This study provides valuable insights into the pathogenesis and treatment of PAH.
本研究旨在揭示肺动脉高压（PAH）的潜在诊断指标，评估免疫细胞在疾病发病机制中的功能，并寻找具有改善预后潜力的创新治疗靶点和药物。我们利用基因表达综合数据库获取 PAH 数据集。我们使用 R 软件识别差异表达基因（DEGs）并研究其功能。采用加权基因共表达网络分析、最小绝对收缩和选择算子以及支持向量机来识别生物标志物。使用 CIBERSORT 确定正常和 PAH 组织中免疫细胞的浸润程度。此外，还分析了诊断标志物与免疫细胞之间的相关性。在这项研究中，使用 258 个 DEGs 来分析疾病本体。大多数 DEGs 与动脉粥样硬化、动脉粥样硬化性心血管疾病和肺部疾病（包括阻塞性肺病）有关。基因集富集分析显示，与正常样本相比，PAH 患者的结果主要与 ECM-受体相互作用、致心律失常性右心室心肌病、Wnt 信号通路和黏附斑有关。FAM171B 被确定为 PAH 的生物标志物（曲线下面积=0.873）。通过对免疫细胞浸润的研究，发现 PAH 的发病机制可能是由幼稚 CD4 T 细胞、静息记忆 CD4 T 细胞、静息 NK 细胞、单核细胞、激活树突状细胞、静息肥大细胞和中性粒细胞介导的。FAM171B 的表达还与静息肥大细胞、单核细胞和 CD8 T 细胞有关。结果表明，PAH 可能与具有高诊断性能的 FAM171B 密切相关，并与免疫细胞浸润有关，提示 FAM171B 可能通过刺激免疫浸润和免疫反应促进 PAH 的进展。本研究为 PAH 的发病机制和治疗提供了有价值的见解。
