Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530007, China.
BMC Med Genomics. 2024 Jan 23;17(1):31. doi: 10.1186/s12920-024-01804-y.
Mechanical ventilation, a critical support strategy for individuals enduring severe respiratory failure and general anesthesia, paradoxically engenders ventilator-induced lung injury (VILI). Ferrostatin-1 mitigates lung injury via ferroptosis inhibition, yet the specific ferroptosis genes contributing significantly to VILI remain obscure.
Leveraging the Gene Expression Omnibus database, we acquired VILI-associated datasets and identified differentially expressed genes (DEGs). To identify the hub genes, we constructed a protein-protein interaction network and used three parameters from CytoHubba. Consequently, we identified hub genes and ferroptosis genes as ferroptosis hub genes for VILI (VFHGs). We conducted enrichment analysis and established receiver operating characteristic (ROC) curves for VFHGs. Subsequently, to confirm the correctness of the VFHGs, control group mice and VILI mouse models, as well as external dataset validation, were established. For further research, a gene-miRNA network was established. Finally, the CIBERSORT algorithm was used to fill the gap in the immune infiltration changes in the lung during VILI.
We identified 64 DEGs and 4 VFHGs (Il6,Ptgs2,Hmox1 and Atf3) closely related to ferroptosis. ROC curves demonstrated the excellent diagnostic performance of VFHGs in VILI. PCR and external dataset validation of the VILI model demonstrated the accuracy of VFHGs. Subsequently, the gene-miRNA network was successfully established. Ultimately, an Immune cell infiltration analysis associated with VILI was generated.
The results emphasize the importance of 4 VFHGs and their involvement in ferroptosis in VILI, confirming their potential as diagnostic biomarkers for VILI.
机械通气是严重呼吸衰竭和全身麻醉患者的关键支持策略，但它会导致呼吸机引起的肺损伤（VILI）。铁抑素-1 通过抑制铁死亡来减轻肺损伤，但导致 VILI 的具体铁死亡基因仍不清楚。
我们利用基因表达综合数据库，获得了与 VILI 相关的数据集，并鉴定了差异表达基因（DEGs）。为了鉴定枢纽基因，我们构建了一个蛋白质-蛋白质相互作用网络，并使用 CytoHubba 的三个参数。因此，我们确定了枢纽基因和铁死亡基因作为 VILI 的铁死亡枢纽基因（VFHGs）。我们进行了富集分析，并为 VFHGs 建立了接收器操作特征（ROC）曲线。随后，为了确认 VFHGs 的正确性，我们建立了对照组小鼠和 VILI 小鼠模型以及外部数据集验证。为了进一步研究，我们建立了一个基因-miRNA 网络。最后，使用 CIBERSORT 算法填补了 VILI 期间肺中免疫浸润变化的空白。
我们鉴定了 64 个 DEGs 和 4 个与铁死亡密切相关的 VFHGs（Il6、Ptgs2、Hmox1 和 Atf3）。ROC 曲线表明 VFHGs 在 VILI 中的诊断性能优异。PCR 和外部数据集验证 VILI 模型表明 VFHGs 的准确性。随后，成功建立了基因-miRNA 网络。最终，生成了与 VILI 相关的免疫细胞浸润分析。
这些结果强调了 4 个 VFHGs 及其在 VILI 中参与铁死亡的重要性，证实了它们作为 VILI 诊断生物标志物的潜力。
