Department of respiratory and critical care medicine, the first affiliated hospital of Anhui medical university, Hefei 230022, China.
Department of Infectious Diseases, Hefei second people's hospital, Hefei 230001, China.
Int J Med Sci. 2022 Aug 15;19(9):1417-1429. doi: 10.7150/ijms.73305. eCollection 2022.
Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease characterized by peripheral distribution of bilateral pulmonary fibrosis that is more pronounced at the base. IPF has a short median survival time and a poor prognosis. Therefore, it is necessary to identify effective prognostic indicators to guide the treatment of patients with IPF. We downloaded microarray data of bronchoalveolar lavage cells from the Gene Expression Omnibus (GEO), containing 176 IPF patients and 20 controls. The top 5,000 genes in the median absolute deviation were classified into different color modules using weighted gene co-expression network analysis (WGCNA), and the modules significantly associated with both survival time and survival status were identified as prognostic modules. We used Lasso Cox regression and multivariate Cox regression to search for hub genes related to prognosis from the differentially expressed genes (DEGs) in the prognostic modules and constructed a risk model and nomogram accordingly. Moreover, based on the risk model, we divided IPF patients into high-risk and low-risk groups to determine the biological functions and immune cell subtypes associated with the prognosis of IPF using gene set enrichment analysis and immune cell infiltration analysis. A total of 153 DEGs located in the prognostic modules, three (TPST1, MRVI1, and TM4SF1) of which were eventually defined as prognostic hub genes. A risk model was constructed based on the expression levels of the three hub genes, and the accuracy of the model was evaluated using time-dependent receiver operating characteristic (ROC) curves. The areas under the curve for 1-, 2-, and 3-year survival rates were 0.862, 0.885, and 0.833, respectively. The results of enrichment analysis showed that inflammation and immune processes significantly affected the prognosis of patients with IPF. The degree of mast and natural killer (NK) cell infiltration also increases the prognostic risk of IPF. We identified three hub genes as independent molecular markers to predict the prognosis of patients with IPF and constructed a prognostic model that may be helpful in promoting therapeutic gains for IPF patients.
特发性肺纤维化(IPF)是一种慢性呼吸系统疾病,其特征为双侧肺纤维化呈周边性分布,基底部更为明显。IPF 的中位生存时间短,预后差。因此,有必要确定有效的预后指标,以指导 IPF 患者的治疗。
我们从基因表达综合数据库(GEO)下载了支气管肺泡灌洗液的微阵列数据,其中包含 176 名 IPF 患者和 20 名对照。使用加权基因共表达网络分析(WGCNA)对中位数绝对偏差中的前 5000 个基因进行分类,将与生存时间和生存状态均显著相关的模块鉴定为预后模块。我们使用 Lasso Cox 回归和多变量 Cox 回归从预后模块中的差异表达基因(DEGs)中搜索与预后相关的枢纽基因,并相应构建风险模型和诺模图。此外,基于风险模型,我们将 IPF 患者分为高危和低危组,以使用基因集富集分析和免疫细胞浸润分析确定与 IPF 预后相关的生物学功能和免疫细胞亚型。
共有 153 个位于预后模块中的 DEGs,其中 3 个(TPST1、MRVI1 和 TM4SF1)最终被定义为预后枢纽基因。基于这 3 个枢纽基因的表达水平构建了一个风险模型,并使用时间依赖性接受者操作特征(ROC)曲线评估模型的准确性。模型对 1、2 和 3 年生存率的曲线下面积分别为 0.862、0.885 和 0.833。富集分析结果表明,炎症和免疫过程显著影响 IPF 患者的预后。肥大细胞和自然杀伤(NK)细胞浸润的程度也增加了 IPF 的预后风险。
我们确定了 3 个枢纽基因作为独立的分子标志物来预测 IPF 患者的预后,并构建了一个预后模型,这可能有助于促进 IPF 患者的治疗效果。