Identification of Crucial Genes in Pathogenesis and Diagnostic Value Analysis of Partial Androgen Insensitivity Syndrome Using Bioinformatics Analysis

Background: Androgen insensitivity syndrome (AIS) is a rare X-linked genetic disease and one of the causes of 46, XY disorder of sexual development. The unstraightforward diagnosis of AIS and gender assignment dilemma still make a plague for this disorder due to the overlapping clinical phenotypes.Methods: Peripheral blood mononuclear cells (PBMCs) of partial AIS patients and healthy controls were separated and underwent RNA-seq to investigate the transcriptome variance. Then, tissue-specific gene expression, functional enrichment, and protein-protein interaction (PPI) network analyses were performed, and the key modules were identified. Finally, RNA expression of differentially expressed genes of interest was validated in PBMCs from PAIS patients and healthy controls by qRT-PCR.Results: In our dataset, a total of 725 differentially expressed genes (DEGs) were captured. The results of functional enrichment analysis indicated that these genes were significantly enriched in reproduction and immune-related pathways and GO functions. It is in accordance with the tissue-specific gene expression analysis of the DEGs with the most highly specific systems centered on the hematologic/immune and reproduction/endocrine. We finally filtered out CCR1, PPBP, PF4, CLU, KMT2D, GP6 and SPARC by the key gene clusters of PPI network and manual screening of tissue-specific gene expression. These novel genes provide insight into the pathogenesis of AIS in the immune or metabolism. In addition, results involving undermasculinization brought forward possible molecular markers for clinical screening. The results of qRT-PCR showed that the trend of expression levels in PAIS patients and healthy controls were consistent with the bioinformatics analysis results.Conclusion: The present study elucidated the molecular mechanisms underlying the pathogenesis and progression of AIS, and provided candidate targets for diagnosis and treatment. However, further investigations into the relationships between these genes and AIS are needed in the future