Ferroptosis-Related Genes in Bronchoalveolar Lavage Fluid Serves as Prognostic Biomarkers for Idiopathic Pulmonary Fibrosis.
Ferroptosis-Related Genes in Bronchoalveolar Lavage Fluid Serves as Prognostic Biomarkers for Idiopathic Pulmonary Fibrosis.
复制标题
支气管肺泡灌洗液中的铁死亡相关基因可作为特发性肺纤维化的预后生物标志物
DOI：
10.3389/fmed.2021.693959
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发表时间：
2021
影响因子：
3.9
通讯作者：
Ren H
中科院分区：
文献类型：
--
作者：
Li M;Wang K;Zhang Y;Fan M;Li A;Zhou J;Yang T;Shi P;Li D;Zhang G;Chen M;Ren H
背景：特发性肺纤维化（IPF）是一种病因不明、预后不良的慢性进行性疾病。铁凋亡是一种调节性细胞死亡的形式，具有铁依赖性方式，参与各种疾病的发展。而铁凋亡相关基因（FRG）在IPF中的预后价值仍不确定，需要进一步阐明。方法：检索FerDb数据库，并结合前人的研究，对FRG进行分析。IPF患者的数据来自GSE 70866数据集。应用Wilcoxon检验和单变量考克斯回归分析来鉴定在正常人和IPF患者之间差异表达并与预后相关的FRG。接下来，在训练组群中通过最小绝对收缩和选择算子（LASSO）惩罚的考克斯模型构建多基因签名，并通过使用校准和受试者工作特征（ROC）曲线进行评估。然后，随机选择30%的数据集样本进行内部验证。最后，进一步探讨了与风险评分相关的差异表达基因（DEGs）可能影响的潜在功能和途径。结果如下：FerrDb数据库和既往研究共鉴定出183个FRG，其中19个FRG在IPF和健康对照者支气管肺泡灌洗液（BALF）中差异表达，并与预后相关（p < 0.05）。有5个FRG（乌头酸酶1 [ACO 1]、神经母细胞瘤RAS病毒（v-ras）癌基因同源物[NRAS]、外核苷酸焦磷酸酶/磷酸二酯酶2 [ENPP 2]、粘蛋白1 [MUC 1]和ZFP 36环指蛋白[ZFP 36]）被确定为风险特征，并将IPF患者分为两个风险组。高危组总生存率明显低于低危组（P < 0.001）。校准和ROC曲线分析证实了该签名的预测能力，并且在验证组中进一步验证了结果。发现与风险评分相关的DEG在ECM-受体相互作用和粘着斑途径中富集。结论：BALF中5种FRG可作为预测IPF预后的指标，有助于改善IPF的治疗策略。
Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated. Methods: The FerrDb database and the previous studies were screened to explore the FRGs. The data of patients with IPF were obtained from the GSE70866 dataset. Wilcoxon's test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and patients with IPF and associated with prognosis. Next, a multigene signature was constructed by the least absolute shrinkage and selection operator (LASSO)-penalized Cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might be affected by the risk score-related differently expressed genes (DEGs) were further explored. Results: A total of 183 FRGs were identified by the FerrDb database and the previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (p < 0.05). There were five FRGs (aconitase 1 [ACO1], neuroblastoma RAS viral (v-ras) oncogene homolog [NRAS], Ectonucleotide pyrophosphatase/phosphodiesterase 2 [ENPP2], Mucin 1 [MUC1], and ZFP36 ring finger protein [ZFP36]) identified as risk signatures and stratified patients with IPF into the two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (p < 0.001). The calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways. Conclusion: The five FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving the management strategies of IPF.