Department of Cardiovascular Surgery, The Affiliated Hospital, Metabolic Vascular Diseases Key Laboratory of Sichuan Province, Key Laboratory of Cardiovascular Remodeling and Dysfunction, Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, P.R. China.
Respir Res. 2024 May 24;25(1):220. doi: 10.1186/s12931-024-02849-4.
Pulmonary arterial hypertension (PAH) is a complex and progressive illness that has a multifaceted origin, significant fatality rates, and profound effects on health. The pathogenesis of PAH is poorly defined due to the insufficient understanding of the combined impact of endoplasmic reticulum (ER) stress and immune infiltration, both of which play vital roles in PAH development. This study aims to identify potential ER stress-related biomarkers in PAH and investigate their involvement in immune infiltration.
The GEO database was used to download gene expression profiles. Genes associated with ER stress were obtained from the MSigDB database. Weighted gene co-expression network analysis (WGCNA), GO, KEGG, and protein-protein interaction (PPI) were utilized to conduct screening of hub genes and explore potential molecular mechanisms. Furthermore, the investigation also delved into the presence of immune cells in PAH tissues and the correlation between hub genes and the immune system. Finally, we validated the diagnostic value and expression levels of the hub genes in PAH using subject-workup characterization curves and real-time quantitative PCR.
In the PAH and control groups, a total of 31 genes related to ER stress were found to be differentially expressed. The enrichment analysis revealed that these genes were primarily enriched in reacting to stress in the endoplasmic reticulum, dealing with unfolded proteins, transporting proteins, and processing proteins within the endoplasmic reticulum. EIF2S1, NPLOC4, SEC61B, SYVN1, and DERL1 were identified as the top 5 hub genes in the PPI network. Immune infiltration analysis revealed that these hub genes were closely related to immune cells. The receiver operating characteristic (ROC) curves revealed that the hub genes exhibited excellent diagnostic efficacy for PAH. The levels of SEC61B, NPLOC4, and EIF2S1 expression were in agreement with the findings of bioinformatics analysis in the PAH group.
Potential biomarkers that could be utilized are SEC61B, NPLOC4, and EIF2S1, as identified in this study. The infiltration of immune cells was crucial to the development and advancement of PAH. This study provided new potential therapeutic targets for PAH.
肺动脉高压（PAH）是一种复杂且进展性的疾病，其发病机制具有多面性，致死率高，对健康有深远影响。由于对内质网（ER）应激和免疫浸润的综合影响认识不足，PAH 的发病机制仍不明确，而这两者在 PAH 的发展中都起着至关重要的作用。本研究旨在确定 PAH 中与 ER 应激相关的潜在生物标志物，并研究它们与免疫浸润的关系。
从 GEO 数据库中下载基因表达谱。从 MSigDB 数据库中获得与 ER 应激相关的基因。采用加权基因共表达网络分析（WGCNA）、GO、KEGG、蛋白质-蛋白质相互作用（PPI）对关键基因进行筛选，探讨潜在的分子机制。此外，还研究了 PAH 组织中免疫细胞的存在情况以及关键基因与免疫系统的相关性。最后，采用受试者工作特征曲线和实时定量 PCR 验证了关键基因在 PAH 中的诊断价值和表达水平。
在 PAH 组和对照组中，共发现 31 个与 ER 应激相关的差异表达基因。富集分析显示，这些基因主要富集在内质网应激反应、未折叠蛋白处理、内质网蛋白质转运和加工等过程。PPI 网络中鉴定出 EIF2S1、NPLOC4、SEC61B、SYVN1 和 DERL1 为前 5 个关键基因。免疫浸润分析显示，这些关键基因与免疫细胞密切相关。ROC 曲线显示，这些关键基因对 PAH 具有良好的诊断效能。PAH 组中 SEC61B、NPLOC4 和 EIF2S1 的表达水平与生物信息学分析结果一致。
本研究发现 SEC61B、NPLOC4 和 EIF2S1 可能是潜在的生物标志物。免疫细胞的浸润对 PAH 的发生和发展至关重要。本研究为 PAH 提供了新的潜在治疗靶点。
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