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. 2022 Oct 7;101(40):e30905.
doi: 10.1097/MD.0000000000030905.

Exploration of hub genes involved in PCOS using biological informatics methods

Fei Zhou  1   2 , Yuling Xing  2 , Tiantian Cheng  2 , Linlin Yang  2 , Huijuan Ma  1   2   3
Affiliations

Exploration of hub genes involved in PCOS using biological informatics methods

Fei Zhou et al. Medicine (Baltimore). .

Abstract

Background: The aim of this study was to find underlying genes and their interaction mechanism crucial to the polycystic ovarian syndrome (PCOS) by analyzing differentially expressed genes (DEGs) between PCOS and non-PCOS subjects.

Methods: Gene expression data of PCOS and non-PCOS subjects were collected from gene expression omnibus (GEO) database. GEO2R were used to calculating P value and logFC. The screening threshold of DEGs was P < .05 and | FC | ≥ 1.2. GO annotation and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis was performed by using DAVID (2021 Update). The protein-protein interaction (PPI) network of DEGs was constructed by using the STRING database, and the hub genes were recognized through Hubba plugin of Cytoscape software.

Results: PCOS and non-PCOS subjects shared a total of 174 DGEs, including 14 upregulated and 160 downregulated genes. The GO biological processes enriched by DEGs mainly involved actin cytoskeleton organization, positive regulation of NF-κB signaling pathway, and positive regulation of canonical Wnt signaling pathway. The DEGs were significantly enriched in cytoplasm, nucleus and cytosol. Their molecular functions mainly focused on protein binding, calmodulin binding and glycerol-3-phosphate dehydrogenase activity. The PI3K/Akt signaling pathway and glycosaminoglycan biosynthesis were highlighted as critical pathways enriched by DEGs. 10 hub genes were screened from the constructed PPI network, of which EGF, FN1 and TLR4 were mainly enriched in the PI3K/Akt signaling pathway.

Conclusion: In this study, a total of 174 DEGs and 10 hub genes were identified as new candidate targets for insulin resistance (IR) in PCOS individuals, which may provide a new direction for developing novel treatment strategies for PCOS.

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Conflict of interest statement

The authors have no funding and conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
The flow diagram of the process of gene differential analysis.
Figure 2.
Figure 2.
Volcano plots and heatmaps of DEGs in GSE6798 and GSE8157. The volcano plots showed the DEGs in the chip compared with normal umbilical cords; red dots represent PCOS highly expressed genes, and blue dots represent PCOS low expressed genes. The heatmaps showed the top 100 genes with the most significant DEGs. Red represents a high expression signal, and blue represents a low expression signal. (A) GSE6798 differential expression gene volcano plot. (B) GSE8157 differential expression gene volcano plot. (C) GSE6798 differential expression gene heatmap. (D) GSE8157 differential expression gene heatmap. DEGs = differentially expressed genes, PCOS = polycystic ovarian syndrome.
Figure 3.
Figure 3.
GO enrichment analysis and KEGG pathway enrichment results of DEGs. The abscissa represents the P value, and the ordinate represents different terms. The larger the dots in the figure, the more genes contained in this term; the redder the dot color, the higher the probability of genes rich in this term. (A) Top 10 enrichment analysis results of BP. (B) Top 10 enrichment analysis results of CC. (C) Top 10 enrichment analysis results of MF. (D) KEGG pathway enrichment results of DEGs. BP = biological processes, CC = cellular component, DEGs = differentially expressed genes, KEGG = Kyoto encyclopedia of genes and genomes, MF = molecular function.
Figure 4.
Figure 4.
PI3K/Akt signaling pathway. Red represents the hub genes we identified in the PI3K/Akt signaling pathway.
Figure 5.
Figure 5.
PPI network of DEGs and hub genes. (A) PPI network of DEGs. Pink nodes represent the interaction among DEGs. Only the 148 DEGs that interact with other ones were demonstrated in the network. (B)Top 10 hub genes identified from the PPI network. From the red nodes to the yellow ones, the connection degree of each molecule with others gradually decreases. DEGs = differentially expressed genes, PPI = protein-protein interaction.
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References

    1. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifes tations that impacts on health across the lifespan. BMC Med. 2010;8:41. - PMC - PubMed
    1. Shen H, Liang Z, Zheng S, Li X. Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome. Int J Mol Med. 2017;40:1385–96. - PMC - PubMed
    1. Ożegowska K, Plewa S, Mantaj U, et al. . Serum metabolomics in PCOS women with different body mass index. J Clin Med. 2021;10:2811. - PMC - PubMed
    1. Dumesic DA, Oberfield SE, Stener-Victorin E, et al. . Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015;36:487–525. - PMC - PubMed
    1. Rodgers RJ, Suturina L, Lizneva D, et al. . Is polycystic ovary syndrome a 20th Century phenomenon? Med Hypotheses. 2019;124:31–4. - PubMed

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