Key result
MAPK6 was identified as a crucial hub gene to discriminate idiopathic pulmonary arterial hypertension from normal controls with an AUC of 100%.
Why the study?
Idiopathic pulmonary arterial hypertension is a life-threatening chronic immune disease with unclear molecular mechanisms and T cell infiltration patterns.
MAPK6 is a crucial hub gene that discriminates idiopathic pulmonary arterial hypertension from normal tissue, highlighting the role of dysregulated T cell immune reactions in the disease.
Answers are grounded in this paper and cite their sources.
Bioinformatics insights into IPAH immune pathways should not change practice; leaves open need for prospective validation.
Background: Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening disease. Growing evidence indicated that IPAH is a chronic immune disease. This study explored the molecular mechanisms and T cell infiltration of IPAH using integrated bioinformatics methods. Methods: Gene expression profiles of dataset GSE113439 were downloaded from the Gene Expression Omnibus and analyzed using R. Protein-protein interaction (PPI) network and gene set enrichment analysis (GSEA) were established by NetworkAnalyst. Gene Ontology enrichment analysis was performed using ClueGO. Transcription factors of differentially expressed genes (DEGs) were estimated using iRegulon. Transcription factors and selected hub genes were verified by real-time polymerase chain reaction (qPCR) in the lung tissues of rats with pulmonary artery hypertension. The least absolute shrinkage and selection operator regression model and the area under the receiver operating characteristic curve (AUC) were applied jointly to identify the crucial hub genes. Moreover, immune infiltration in IPAH was calculated using ImmuCellAI, and the correlation between key hub genes and immune cells was analyzed using R. Results: A total of 512 DEGs were screened, and ten hub genes and three transcription factors were filtered by the DEG PPI network. The DEGs were mainly enriched in mitotic nuclear division, chromosome organization, and nucleocytoplasmic transport. The ten hub genes and three transcription factors were confirmed by qPCR. Moreover, MAPK6 was identified as the most potent biomarker with an AUC of 100%, and ImmuCellAI immune infiltration analysis showed that a higher proportion of CD4-naive T cells and central memory T cells (Tcm) was apparent in the IPAH group, whereas the proportions of cytotoxic T cells (Tc), exhausted T cells (Tex), type 17 T helper cells, effector memory T cells, natural killer T cells (NKT), natural killer cells, gamma-delta T cells, and CD8 T cells were lower. Finally, MAPK6 was positively correlated with Tex and Tcm, and negatively correlated with Tc and NKT. Conclusion:MAPK6 was identified as a crucial hub gene to discriminate IPAH from the normal group. Dysregulated immune reactions were identified in the lung tissue of patients with IPAH.
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Yang et al. (2022) studied Idiopathic pulmonary arterial hypertension (IPAH). MAPK6 expression vs. Normal group was evaluated on Discrimination of IPAH from normal group (AUC 100%). MAPK6 was identified as a crucial hub gene to discriminate idiopathic pulmonary arterial hypertension from normal controls with an AUC of 100%.
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