Affiliation:
1. Affiliated Hospital of Jiangnan University
2. Jiangnan University
Abstract
Abstract
Background
Polycystic ovary syndrome (PCOS) is a common female endocrinal disease that may result in excessive androgen, but the mechanism of PCOS remains unclear. Most patients with PCOS suffer from low-grade inflammation, whereas the underlying connection between immune and PCOS is still uncertain.
Objective
This study aimed to determine the immune-related mechanisms behind PCOS pathogenesis and explore distinct immune-related genes and their functional signatures in PCOS.
Methods
The microarray dataset GSE155489 was downloaded from the Gene Expression Omnibus (GEO) database. The immune-related genes were downloaded from ImmPort. The immune-related differential expression genes (IRDEGs) in PCOS were screened, and functional and pathway enrichment analyses were applied. The protein-protein interactions (PPI), module analysis, and transcription factor enrichment analysis (TFEA) were used to identify hub genes. The immune profile analysis was depicted, and the expression correlation analysis between hub genes and m6A modifiers in PCOS was constructed.
Results
125 IRDEGs were identified, and immune-related pathways included the cytokine-cytokine receptor pathway, T cell receptor signaling pathway, and TNF signaling pathway. All genes were associated with four immune cells (monocyte cells, nTreg, iTreg, and Tcm). Moreover, Major Histocompatibility Complex, Class I, A (HLA-A), Major Histocompatibility Complex, Class I, B (HLA-B), Fos Proto-Oncogene (FOS), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), and C-X-C Motif Chemokine Receptor 4 (CXCR4) were identified as hub genes. Furthermore, N6-Methyladenosine (m6A methylation) mediators could potentially play a pivotal role between the immune system and PCOS.
Conclusion
This study described the relevance between immune and PCOS. We identified five IRDEGs as hub genes for PCOS. The relationship between the m6A methylation and hub genes indicated that m6A methylation could play a potential role in regulating such hub genes in PCOS. These findings could provide new insights into the molecular mechanisms and diagnosis or treatment strategy for the disease.
Publisher
Research Square Platform LLC
Reference73 articles.
1. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis;Barry JA;Hum Reprod Update,2014
2. Criteria, prevalence, and phenotypes of polycystic ovary syndrome;Lizneva D;Fertility and Sterility. 2016 Jul
3. Barber TM, Kyrou I, Randeva HS, Weickert MO. Mechanisms of Insulin Resistance at the Crossroad of Obesity with Associated Metabolic Abnormalities and Cognitive Dysfunction. Int J Mol Sci. 2021 Jan 7;22(2):E546.
4. Genetic, hormonal and metabolic aspects of PCOS: an update;Leo V;Reprod Biol Endocrinol. 2016 Jul
5. Dabravolski SA, Nikiforov NG, Eid AH, Nedosugova LV, Starodubova AV, Popkova TV, et al. Mitochondrial Dysfunction and Chronic Inflammation in Polycystic Ovary Syndrome. Int J Mol Sci. 2021 Apr 10;22(8):3923.