Identification of key genes and immune profile in limited cutaneous systemic sclerosis-associated pulmonary arterial hypertension by bioinformatics analysis

Aims: Limited cutaneous systemic sclerosis-associated pulmonary arterial hypertension (lcSSc-PAH) is a complex multi-system disease with high morbidity and mortality. The purpose of this study is to identify the hub genes and immune characteristics of limited cutaneous systemic sclerosis (lcSSc) and lcSSc-PAH through bioinformatics.

Main methods: LcSSc-PAH raw data were obtained from the GEO database (GSE19617). Weighted gene Co-expression Network analysis (WGCNA) was used to evaluate key modules. Then, we performed Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis with R software and verified the diagnostic value of the hub genes. Finally, Immune Cell Abundance Identifier (ImmuCellAI) was used to analyze the immune characteristics of the normal subjects, lcSSc and lcSSc-PAH patients, the results were displayed graphically.

Key findings: Enrichment of two important modules by GO and KEGG identified key biological processes and pathways related to pathogen infection and immune function. Three hub genes (BID, IFNGR1, ZAP70) related to immune function were identified. The analysis of immune characteristics showed that the correlation and abundance of immune cells such as inducible regulatory T (iTreg) cells, B cells, macrophages, natural killer (NK) cells, CD8T cells, mucosal-associated invariant T(MAIT) cells and dendritic cells(DCs) were significantly different in the normal subjects, lcSSc and lcSSc-PAH patients.

Significance: Pathogen infection, changes in the number and function of immune cells, and interactions among immune cells may preliminarily reveal the pathological mechanism of lcSSc-PAH. The hub genes, pathways and immune characteristics identified in this research remains to be further studied.