Bioinformatic analysis identifies the immunological profile of turner syndrome with different X chromosome origins

Abstract

IntroductionTurner syndrome (TS) is a chromosomal disorder that affects phenotypic females who have one intact X chromosome and complete or partial absence of the second sex chromosome in association with one or more clinical manifestations. However, the immunological profile of TS with different X chromosome origins is incompletely understood.MethodsIn this study, transcriptomic expression profiles of 26 TS (45,X) samples and 10 normal karyotype (46,XX) samples derived from GSE46687 cohort were employed. Differentially expressed immune-related genes (DEIRGs) between monosomy X TS patients with different X chromosome origins and normal females were investigated respectively. Subsequently, functional annotation, protein-protein interaction (PPI) network analysis, immunocyte infiltration evaluation, tissue-specific gene expression and Weighted gene co expression network analysis (WGCNA) were performed to explore the immunological characteristic in TS with different X chromosome origins.Results34 and 52 DEIRGs were respectively identified in 45,Xm and 45,Xp patients compared with normal individuals. The identified DEIRGs in Xm group were significantly enriched in pathways associated with cancer. In Xp TS patients, the most enriched signals were immune response-related. A majority of genes involved in the above pathways were downregulated. PPI analysis identified 4 (FLT3, IL3RA, CSF2RA, PIK3R3) and 6 (PDGFRB, CSF2, IL5, PRL, CCL17 and IL2)hub genes for Xm and Xp groups, respectively. CIBERSORT results showed that the proportion of Tregs in the Xm group and the naive B cells and resting NK cells in the Xp group significantly increased, respectively. Tissue-specific expression results indicated that BDCA4+_dentritic cells and CD19+ B cells were the prominent specific expressed tissues in Xp patients. Results of WGCNA support the above analysis.ConclusionsThis study aims at studying the immunological characteristics of TS with different X chromosome origins. Pathways in cancer in Xm group and immune response in Xp group were suppressed. 4 and 6 hub IRGs were identified as biomarkers for Xm and Xp patients, respectively. B cells played important roles in Xp patients. Further studies are needed to draw more attention to the functional validation of these hub genes and the roles of B cells.

The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development

“…Immune regulation within the fetal-placental interface is emerging as a key mechanism in pregnancy maintenance, and CSF2RA has been proposed as a candidate gene for early lethality in 45,X embryos 2,6 . CSF2RA has been shown to have 10-fold lower expression in 45,X-derived human embryonic stem cells compared to 46,XX-derived controls, and reduced expression in BDCA4+ dendritic cells from women with TS 6,59 . CSF2RA is implicated in placental development 60 , and studies in bovine cultured embryos suggest CSF2 promotes embryo survival through antiapoptotic effects and by signaling of developmental pathways 61 .…”

Organ Abnormalities Caused by Turner Syndrome

“…The CSF2RA (colony-stimulating factor 2 receptor alpha) gene located in the pseudoautosomal region 1 (PAR1) of the X chromosome is possibly involved in intrauterine lethality in fetuses with 45,X TS [21]. CSF2RA expression is downregulated in placental cells of females with 45,X TS compared with that in controls [13,22]. USP9X (located in Xp11.4) is a candidate for the failure of gonadal and oocyte development in TS [53].…”