Department of Stem Cell and Regenerative Medicine, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, 400010, Chongqing, China.
Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, 400010, Chongqing, China.
Comb Chem High Throughput Screen. 2024;27(1):168-185. doi: 10.2174/1386207326666230510095840.
High altitude pulmonary edema (HAPE) is a serious mountain sickness with certain mortality. Its early diagnosis is very important. However, the mechanism of its onset and progression is still controversial.
This study aimed to analyze the HAPE occurrence and development mechanism and search for prospective biomarkers in peripheral blood.
The difference genes (DEGs) of the Control group and the HAPE group were enriched by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and then GSEA analysis was performed. After identifying the immune-related hub genes, QPCR was used to verify and analyze the hub gene function and diagnostic value with single-gene GSEA and ROC curves, and the drugs that acted on the hub gene was found in the CTD database. Immune infiltration and its association with the hub genes were analyzed using CIBERSORT. Finally, WGCNA was employed to investigate immune invasion cells' significantly related gene modules, following enrichment analysis of their GO and KEGG.
The dataset enrichment analysis, immune invasion analysis and WGCNA analysis showed that the occurrence and early progression of HAPE were unrelated to inflammation. The hub genes associated with immunity obtained with MCODE algorithm of Cytoscape were JAK2 and B2M.. RT-qPCR and ROC curves confirmed that the hub gene B2M was a specific biomarker of HAPE and had diagnostic value, and single-gene GSEA analysis confirmed that it participated in MHC I molecule-mediated antigen presentation ability decreased, resulting in reduced immunity.
Occurrence and early progression of high altitude pulmonary edema may not be related to inflammation. B2M may be a new clinical potential biomarker for HAPE for early diagnosis and therapeutic evaluation as well as therapeutic targets, and its decrease may be related to reduced immunity due to reduced ability of MCH I to participate in antigen submission.
高原肺水肿（HAPE）是一种严重的高山病，具有一定的死亡率。其早期诊断非常重要。但其发病和进展机制仍存在争议。
本研究旨在分析 HAPE 的发生发展机制，寻找外周血中的潜在生物标志物。
通过基因本体（GO）、京都基因与基因组百科全书（KEGG）富集分析对对照组和 HAPE 组的差异基因（DEGs）进行富集，然后进行 GSEA 分析。鉴定出免疫相关的枢纽基因后，采用 QPCR 对枢纽基因功能进行验证和分析，通过单基因 GSEA 和 ROC 曲线分析其诊断价值，并在 CTD 数据库中查找作用于枢纽基因的药物。采用 CIBERSORT 分析免疫浸润及其与枢纽基因的关系。最后，利用 WGCNA 分析免疫浸润细胞的显著相关基因模块，并对其进行 GO 和 KEGG 富集分析。
数据集富集分析、免疫浸润分析和 WGCNA 分析表明，HAPE 的发生和早期进展与炎症无关。Cytoscape 的 MCODE 算法获得的与免疫相关的枢纽基因是 JAK2 和 B2M。RT-qPCR 和 ROC 曲线证实，枢纽基因 B2M 是 HAPE 的特异性生物标志物，具有诊断价值，单基因 GSEA 分析证实其参与 MHC I 分子介导的抗原呈递能力下降，导致免疫功能下降。
高原肺水肿的发生和早期进展可能与炎症无关。B2M 可能是 HAPE 的一种新的临床潜在生物标志物，可用于早期诊断和治疗评估以及治疗靶点，其减少可能与 MHC I 参与抗原呈递能力下降导致的免疫功能下降有关。
