NAFLD and PCOS,pathogenesis being similarly,are highly prevalent diseases in the world.In this study, to explore the molecular mechanisms in these 2 diseases and discover the early targets to prevent disease development,through searching the datasets of NAFLD and PCOS from GEO, we find 34 common genes including 1mirRNA-mir223. After we perform GO enrichment and KEGG pathway enrichment analyses and construct a PPI network ,top 6 among 21 key genes found by above analysis represent a good diagnostic value in PCOS patients .
Matrix metalloproteinase-9(MMP9) may play an essential role in PCOS and NAFLD.A study  proves that PCOS patients have elevated serum concentrations of MMP-2 and MMP-9.Anotherproves that MMP9 may be involved in the pathogenesis of PCOS and matrix metalloproteinases (MMPs) play vital roles in follicular development.A recent studymakes a rat model of PCOS and proves that metformin treatment by decreasing the expression of MMP-2 and MMP-9 alleviates PCOS.Anotherproves that MMP-9 levels are increased in obese PCOS women. Moreover,studymade a rodent model of non-alcoholic steatohepatitis present that MMP-9 activity is negatively correlates with adiponectin—which can protect from inflammation and fibrosis in metabolic liver disease.Besides,study proves that MMP-9 deficiency enhances regeneration of steatotic livers.Studyproves that MMP9 levels can act as predictive factors for poor prognosis of nonalcoholic fatty liver patients .
Formyl peptide receptor 1(FPR1) is powerful neutrophil chemotactic factors. Binding receptor stimulates intracellular calcium mobilization and superoxide anion release. A review —decoding cell death signals in liver inflammation, points out that FPR1 by mitochondrial damage, potent neutrophil activators and plasma membrane permeabilization causes liver inflammation.However,the study of the relationship between FPR1 and PCOS has not been found.
S100A9 plays a vital role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion and increase the bactericidal activity of neutrophils by promoting phagocytosis. A study observes that PCOS follicular fluid exosomes contain S100-A9 protein which can enhance inflammation and disrupt steroidogenesis via activation of nuclear factor kappa B signalling pathway. The study of the relationship between S100A9 and NAFLD has not been found.
Triggering receptor expressed on myeloid cells 1(TREM1) stimulates neutrophil, monocyte-mediated inflammatory responses and triggers release of pro-inflammatory chemokines and cytokines, as well as increase surface expression of cell activation markers.Studyproves that TREM-1 is upregulation at messenger RNA and protein levels in NAFLD model mice.The study of the relationship between TREM1 and PCOS has not been found.
Intercellular adhesion molecule 1(ICAM1) is ligands for the leukocyte adhesion protein integrin alpha-L/beta-2.During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups.Studyproves that the patients with PCOS and NAFLD are heavier cardiovascular risk profile compared with patients with PCOS involving serum markers(ICAM-1).ICAM1 in NAFLD and PCOS need further exploration.
S100A12,which is similar to S100A9, may play a prominent role in inflammatory processes and immune response. It can act as an alarmin or a danger associated molecular pattern molecule and stimulate innate immune cells via binding to receptor for advanced glycation endproducts (AGER),which can activate the MAP-kinase and NF-kappa-B signaling pathways.It's worth noting that it needs further research to confirm in PCOS and NAFLD.
For mir-223,some researches focus on relationship between PCOS and mir-223[41–47]. Moreover,others draw on relationship between NAFLD and mir-223[48–56].In this study,we find the mir-223 as the common gene between PCOS and NAFLD.Our research also indicated that mir-223 might become a potential target in PCOS and NAFLD treatment.
Besides,we performed gene biological functions and pathways, such as inflammatory reactions,NF-kappa B signaling pathway, which are closely involved in 2 diseases.Meanwhile there coexist advantages and disadvantages in this study. For disadvantages, the included samples are relatively small, key genes predicted need larger-sample, experimental and clinical research to verify.For advantages,we explore and analyze the top 6 key genes and 1 common gene. The AUC calculated by the top 6 key genes in the PCOS is 0.909 (95% CI, 0.775–1.000), showing a good diagnostic efficiency. Importantly,we point out the direction of future research for PCOS and NAFLD from molecular level.