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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Identification of Hub Genes and Biomarkers between Hyperandrogen and Normoandrogen Polycystic Ovary Syndrome by Bioinformatics Analysis

Author(s): Tianwei Zhang, Yang Liu, Xiaodong Li* and Baoshan Hu*

Volume 26, Issue 1, 2023

Published on: 27 May, 2022

Page: [126 - 134] Pages: 9

DOI: 10.2174/1386207325666220404101009

Price: $65

Abstract

Background: The common and divergent genetic mechanisms of hyperandrogen (HA) and normoandrogen (NA) polycystic ovary syndrome (PCOS) are currently unknown.

Objective: This study aimed to explore the hub genes and potential mechanisms of HA and NA PCOS through bioinformatics analysis.

Methods: The GSE137684 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The co-expressed genes and differentially expressed genes (DEGs) between HA and NA PCOS samples were functionally annotated by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The protein-protein interaction (PPI) network of the DEGs was constructed and visualized using STRING and Cytoscape, respectively, and the hub genes were screened using the Cytohubba plug-in. The transcription factors (TFs) of these hub genes were identified with the JASPAR database, and the hub gene-TF regulatory network was constructed.

Results: A total of 327 DEGs, including 191 upregulated and 136 downregulated genes, were identified in HA PCOS relative to NA PCOS. Ten hub genes were screened, of which MYC, CAV1, and HGF were mainly enriched in the Proteoglycans in the cancer pathway. In addition, 47 TFs were identified that were found to be involved in the regulation of hub genes.

Conclusion: MYC, CAV1, and HGF are potential diagnostic biomarkers and therapeutic targets for HA PCOS.

Keywords: PCOS, normoandrogen, hyperandrogen, hub gene, biomarker, GEO.

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[1]
Azziz, R. Introduction: Determinants of polycystic ova-ry syndrome. Fertil. Steril., 2016, 106(1), 4-5.
[http://dx.doi.org/10.1016/j.fertnstert.2016.05.009] [PMID: 27238627]
[2]
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic cri-teria and long-term health risks related to polycystic ovary syndrome. Fertil. Steril., 2004, 81(1), 19-25.
[http://dx.doi.org/10.1016/j.fertnstert.2003.10.004] [PMID: 14711538]
[3]
Sung, Y-A.; Oh, J-Y.; Chung, H.; Lee, H. Hyperandrogenemia is implicated in both the metabolic and reproductive morbidi-ties of polycystic ovary syndrome. Fertil. Steril., 2014, 101(3), 840-845.
[http://dx.doi.org/10.1016/j.fertnstert.2013.11.027] [PMID: 24424368]
[4]
Louwers, Y.V.; Laven, J.S.E. Characteristics of polycystic ovary syndrome throughout life. Ther Adv Reprod Health., 2020, 14, 2633494120911038.
[http://dx.doi.org/10.1177/2633494120911038] [PMID: 32518918]
[5]
Doroszewska, K.; Milewicz, T. Mrozińska, S.; Janeczko, J.; Rokicki, R.; Janeczko, M.; Warzecha, D.; Marianowski, P. Blood pressure in postmenopausal women with a history of polycystic ovary syndrome. Przegl. Menopauz., 2019, 18(2), 94-98.
[http://dx.doi.org/10.5114/pm.2019.84039] [PMID: 31485206]
[6]
Huang, R.; Zheng, J.; Li, S.; Tao, T.; Ma, J.; Liu, W. Charac-teristics and contributions of hyperandrogenism to insulin re-sistance and other metabolic profiles in polycystic ovary syn-drome. Acta Obstet. Gynecol. Scand., 2015, 94(5), 494-500.
[http://dx.doi.org/10.1111/aogs.12612] [PMID: 25711494]
[7]
Yang, D.; He, Y.; Wu, B.; Deng, Y.; Wang, N.; Li, M.; Liu, Y. Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer. J. Ovarian Res., 2020, 13(1), 10.
[http://dx.doi.org/10.1186/s13048-020-0613-2] [PMID: 31987036]
[8]
Lin, Y.; Li, J.; Wu, D.; Wang, F.; Fang, Z.; Shen, G. Identifica-tion of hub genes in type 2 diabetes mellitus using bioinfor-matics analysis. Diabetes Metab. Syndr. Obes., 2020, 13, 1793-1801.
[http://dx.doi.org/10.2147/DMSO.S245165] [PMID: 32547141]
[9]
Zeng, Z.; Lin, X.; Xia, T.; Liu, W.; Tian, X.; Li, M. Identifica-tion of crucial lncRNAs, miRNAs, mRNAs, and potential therapeutic compounds for polycystic ovary syndrome by bi-oinformatics analysis. BioMed Res. Int., 2020, 2020, 1817094.
[http://dx.doi.org/10.1155/2020/1817094] [PMID: 33224973]
[10]
Lidaka, L.; Bekere, L.; Rota, A.; Isakova, J.; Lazdane, G.; Kivite-Urtane, A.; Dzivite-Krisane, I.; Kempa, I.; Dobele, Z.; Gailite, L. Role of single nucleotide variants in FSHR, GNRHR, ESR2 and LHCGR genes in adolescents with poly-cystic ovary syndrome. Diagnostics (Basel), 2021, 11(12), 2327.
[http://dx.doi.org/10.3390/diagnostics11122327] [PMID: 34943568]
[11]
Wang, D.; Weng, Y.; Zhang, Y.; Wang, R.; Wang, T.; Zhou, J.; Shen, S.; Wang, H.; Wang, Y. Exposure to hyperandrogen drives ovarian dysfunction and fibrosis by activating the NLRP3 inflammasome in mice. Sci. Total Environ., 2020, 745, 141049.
[http://dx.doi.org/10.1016/j.scitotenv.2020.141049] [PMID: 32758727]
[12]
Aflatounian, A.; Edwards, M.C.; Rodriguez Paris, V.; Ber-toldo, M.J.; Desai, R.; Gilchrist, R.B.; Ledger, W.L.; Handels-man, D.J.; Walters, K.A. Androgen signaling pathways driving reproductive and metabolic phenotypes in a PCOS mouse model. J. Endocrinol., 2020, 245(3), 381-395.
[http://dx.doi.org/10.1530/JOE-19-0530] [PMID: 32229702]
[13]
Zhang, Y.; Weng, Y.; Wang, D.; Wang, R.; Wang, L.; Zhou, J.; Shen, S.; Wang, H.; Wang, Y. Curcumin in combination with aerobic exercise improves follicular dysfunction via inhibi-tion of the hyperandrogen-induced IRE1α/XBP1 endoplasmic reticulum stress pathway in PCOS-like rats. Oxid. Med. Cell. Longev., 2021, 2021, 7382900.
[http://dx.doi.org/10.1155/2021/7382900] [PMID: 34987702]
[14]
Wang, J.; Wu, D.; Guo, H.; Li, M. Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syn-drome. Life Sci., 2019, 236, 116940.
[http://dx.doi.org/10.1016/j.lfs.2019.116940] [PMID: 31604107]
[15]
Shaaban, Z.; Khoradmehr, A.; Amiri-Yekta, A.; Nowzari, F.; Jafarzadeh Shirazi, M.R.; Tamadon, A. Pathophysiologic mechanisms of insulin secretion and signaling-related genes in etiology of polycystic ovary syndrome. Genet. Res., 2021, 2021, 7781823.
[http://dx.doi.org/10.1155/2021/7781823] [PMID: 34949963]
[16]
Rasool, S.U.A.; Ashraf, S.; Nabi, M.; Masoodi, S.R.; Fazili, K.M.; Amin, S. Clinical manifestations of hyperandrogenism and ovulatory dysfunction are not associated with His1058 C/T SNP (rs1799817) polymorphism of insulin receptor gene tyrosine kinase domain in kashmiri women with PCOS. Int. J. Endocrinol., 2021, 2021, 7522487.
[http://dx.doi.org/10.1155/2021/7522487] [PMID: 34912452]
[17]
Palomba, S.; de Wilde, M.A.; Falbo, A.; Koster, M.P.; La Sala, G.B.; Fauser, B.C. Pregnancy complications in women with polycystic ovary syndrome. Hum. Reprod. Update, 2015, 21(5), 575-592.
[http://dx.doi.org/10.1093/humupd/dmv029] [PMID: 26117684]
[18]
Zhang, Y.; Hu, M.; Jia, W.; Liu, G.; Zhang, J.; Wang, B.; Li, J.; Cui, P.; Li, X.; Lager, S.; Sferruzzi-Perri, A.N.; Han, Y.; Liu, S.; Wu, X.; Brännström, M.; Shao, L.R.; Billig, H. Hyper-androgenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats. J. Endocrinol., 2020, 246(3), 247-263.
[http://dx.doi.org/10.1530/JOE-20-0155] [PMID: 32590339]
[19]
Allen-Petersen, B.L.; Sears, R.C. Mission possible: Advances in MYC therapeutic targeting in cancer. BioDrugs, 2019, 33(5), 539-553.
[http://dx.doi.org/10.1007/s40259-019-00370-5] [PMID: 31392631]
[20]
Garcia-Reyero, N.; Villeneuve, D.L.; Kroll, K.J.; Liu, L.; Or-lando, E.F.; Watanabe, K.H.; Sepúlveda, M.S.; Ankley, G.T.; Denslow, N.D. Expression signatures for a model androgen and antiandrogen in the fathead minnow (Pimephales prome-las) ovary. Environ. Sci. Technol., 2009, 43(7), 2614-2619.
[http://dx.doi.org/10.1021/es8024484] [PMID: 19452925]
[21]
Rosselot, C.; Kumar, A.; Lakshmipathi, J.; Zhang, P.; Lu, G.; Katz, L.S.; Prochownik, E.V.; Stewart, A.F.; Lambertini, L.; Scott, D.K.; Garcia-Ocaña, A. Myc Is required for adaptive β-cell replication in young mice but Is not sufficient in one-year-old mice fed with a high-fat diet. Diabetes, 2019, 68(10), 1934-1949.
[http://dx.doi.org/10.2337/db18-1368] [PMID: 31292135]
[22]
Nwosu, Z.C.; Ebert, M.P.; Dooley, S.; Meyer, C. Caveolin-1 in the regulation of cell metabolism: A cancer perspective. Mol. Cancer, 2016, 15(1), 71.
[http://dx.doi.org/10.1186/s12943-016-0558-7] [PMID: 27852311]
[23]
Méndez-Giménez, L.; Rodríguez, A.; Balaguer, I.; Frühbeck, G. Role of aquaglyceroporins and caveolins in energy and metabolic homeostasis. Mol. Cell. Endocrinol., 2014, 397(1-2), 78-92.
[http://dx.doi.org/10.1016/j.mce.2014.06.017] [PMID: 25008241]
[24]
McCracken, E.; Monaghan, M.; Sreenivasan, S. Pathophysiol-ogy of the metabolic syndrome. Clin. Dermatol., 2018, 36(1), 14-20.
[http://dx.doi.org/10.1016/j.clindermatol.2017.09.004] [PMID: 29241747]
[25]
de Souza, G.M.; de Albuquerque Borborema, M.E.; de Lu-cena, T.M.C.; da Silva Santos, A.F.; de Lima, B.R.; de Oliveira, D.C.; de Azevêdo Silva, J. Caveolin-1 (CAV-1) up regulation in metabolic syndrome: All roads leading to the same end. Mol. Biol. Rep., 2020, 47(11), 9245-9250.
[http://dx.doi.org/10.1007/s11033-020-05945-y] [PMID: 33123955]
[26]
Maurya, V.K.; Sangappa, C.; Kumar, V.; Mahfooz, S.; Singh, A.; Rajender, S.; Jha, R.K. Expression and activity of Rac1 is negatively affected in the dehydroepiandrosterone induced polycystic ovary of mouse. J. Ovarian Res., 2014, 7(1), 32.
[http://dx.doi.org/10.1186/1757-2215-7-32] [PMID: 24628852]
[27]
Guglielmo, M.C.; Ricci, G.; Catizone, A.; Barberi, M.; Galdieri, M.; Stefanini, M.; Canipari, R. The effect of hepato-cyte growth factor on the initial stages of mouse follicle de-velopment. J. Cell. Physiol., 2011, 226(2), 520-529.
[http://dx.doi.org/10.1002/jcp.22361] [PMID: 20683913]
[28]
Wei, W.; Kong, B.; Qu, X. Alteration of HGF and TSP-1 ex-pression in ovarian carcinoma associated with clinical fea-tures. J. Obstet. Gynaecol. Res., 2012, 38(1), 57-64.
[http://dx.doi.org/10.1111/j.1447-0756.2011.01695.x] [PMID: 22136730]
[29]
Huang, Y.-L.; Shen, J. Effect of qilin pill combined metformin on polycystic ovaries induced infertility patients. Zhongguo Zhong xi yi jie he za zhi, 2016, 36(9), 1042-1045.
[30]
Mattiske, D.; Kume, T.; Hogan, B.L. The mouse forkhead gene Foxc1 is required for primordial germ cell migration and antral follicle development. Dev. Biol., 2006, 290(2), 447-458.
[http://dx.doi.org/10.1016/j.ydbio.2005.12.007] [PMID: 16412416]
[31]
Shang, Y-K.; Li, C.; Liu, Z-K.; Kong, L-M.; Wei, D.; Xu, J.; Wang, Z-L.; Bian, H.; Chen, Z-N. System analysis of the regu-lation of the immune response by CD147 and FOXC1 in can-cer cell lines. Oncotarget, 2018, 9(16), 12918-12931.
[http://dx.doi.org/10.18632/oncotarget.24161] [PMID: 29560120]
[32]
Pashaiasl, M.; Ebrahimi, M.; Ebrahimie, E. Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis. Mol. Biol. Rep., 2016, 43(9), 923-937.
[http://dx.doi.org/10.1007/s11033-016-4025-8] [PMID: 27324248]

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