Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, Republic of Korea.
Respir Res. 2024 Aug 14;25(1):310. doi: 10.1186/s12931-024-02946-4.
The genetic signatures associated with the susceptibility to nontuberculous mycobacterial pulmonary disease (NTM-PD) are still unknown. In this study, we performed RNA sequencing to explore gene expression profiles and represent characteristic factor in NTM-PD.
Peripheral blood samples were collected from patients with NTM-PD and healthy individuals (controls). Differentially expressed genes (DEGs) were identified by RNA sequencing and subjected to functional enrichment and immune cell deconvolution analyses.
We enrolled 48 participants, including 26 patients with NTM-PD (median age, 58.0 years; 84.6% female), and 22 healthy controls (median age, 58.5 years; 90.9% female). We identified 21 upregulated and 44 downregulated DEGs in the NTM-PD group compared to those in the control group. NTM infection did not have a significant impact on gene expression in the NTM-PD group compared to the control group, and there were no differences in the proportion of immune cells. However, through gene ontology (GO), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) analysis, we discovered that PARK2 is a key factor associated with NTM-PD. The PARK2 gene, which is linked to the ubiquitination pathway, was downregulated in the NTM-PD group (fold change, - 1.314, P = 0.047). The expression levels of PARK2 remained unaltered after favorable treatment outcomes, suggesting that the gene is associated with host susceptibility rather than with the outcomes of infection or inflammation. The area under the receiver operating characteristic curve for the PARK2 gene diagnosing NTM-PD was 0.813 (95% confidence interval, 0.694-0.932).
We identified the genetic signatures associated with NTM-PD in a cohort of Korean patients. The PARK2 gene presents as a potential susceptibility factor in NTM-PD .
与非结核分枝杆菌肺病（NTM-PD）易感性相关的遗传特征尚不清楚。在这项研究中，我们进行了 RNA 测序，以探索 NTM-PD 的基因表达谱和特征因子。
收集 NTM-PD 患者和健康个体（对照）的外周血样本。通过 RNA 测序鉴定差异表达基因（DEGs），并进行功能富集和免疫细胞去卷积分析。
我们共纳入 48 名参与者，包括 26 名 NTM-PD 患者（中位年龄 58.0 岁，84.6%为女性）和 22 名健康对照（中位年龄 58.5 岁，90.9%为女性）。与对照组相比，NTM-PD 组有 21 个上调和 44 个下调的 DEGs。与对照组相比，NTM 感染对 NTM-PD 组的基因表达没有显著影响，免疫细胞的比例也没有差异。然而，通过基因本体（GO）、基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）分析，我们发现 PARK2 是与 NTM-PD 相关的关键因素。与泛素化途径相关的 PARK2 基因在 NTM-PD 组下调（倍数变化，-1.314，P=0.047）。在有利的治疗结果后，PARK2 基因的表达水平保持不变，表明该基因与宿主易感性相关，而与感染或炎症的结果无关。PARK2 基因诊断 NTM-PD 的受试者工作特征曲线下面积为 0.813（95%置信区间，0.694-0.932）。
我们在韩国患者队列中鉴定了与 NTM-PD 相关的遗传特征。PARK2 基因是 NTM-PD 的潜在易感因素。
