Identification of key pathways, genes and immune cell infiltration in hypoxia of high-altitude acclimatization via meta-analysis and integrated bioinformatics analysis

Abstract

Background: For individuals acutely exposed to high-altitude regions, environmental hypobaric hypoxia induces several physiological or pathological responses, especially immune dysfunction. Therefore, hypoxia is a potentially life-threatening factor, which has closely related to high-altitude acclimatization. However, its specific molecular mechanism is still unclear.Methods: The four expression profiles about hypoxia and high altitude were downloaded from the Gene Expression Omnibus database in this study. Meta-analysis of GEO datasets was performed by NetworkAnalyst online tool. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) enrichment analysis, and visualization were performed using R (version 4.1.3) software, respectively. The CIBERSORT analysis was conducted on GSE46480 to examine immune cell infiltration. In addition, we experimentally verified the bioinformatics analysis with qRT-PCR.Results: The meta-analysis identified 358 differentially expressed genes (DEGs), with 209 upregulated and 149 downregulated. DEGs were mostly enriched in biological processes and pathways associated with hypoxia acclimatization at high altitudes, according to both GO and KEGG enrichment analyses. ERH, VBP1, BINP3L, TOMM5, PSMA4, and POLR2K were identified by taking intersections of the DEGs between meta-analysis and GSE46480 and verified by qRT-PCR experiments, which were inextricably linked to hypoxia. Immune infiltration analysis showed significant differences in immune cells between samples at sea level and high altitudes.Conclusion: Identifying the DEGs and pathways will improve our understanding of immune function during high-altitude hypoxia at a molecular level. Targeting hypoxia-sensitive pathways in immune cells is interesting in treating high-altitude sickness. This study provides support for further research on high-altitude acclimatization.

The effect of altitude on the expression of immune-related genes in Peruvian rural indigenous

“…A recent study published by Li et al presents a meta-analysis and bioinformatics approach to available databases to identify which immune genes and how they varied in expression when exposed to altitude conditions. The databases used by these authors were from studies of cells exposed to normoxia or hypoxia, and in the bioinformatics analysis, the cells came from European descent subjects exposed to altitude but not native residents of a high-altitude area (26). Li et al demonstrated that the genes ERH, VBP1, PSMA4, TOMM5, BNIP3L, and POLR2K had a downregulation when associated with hypoxia, except for BNIP3L.…”