A Systematic Review of the Molecular Mechanisms Involved in the Association Between PCOS and Endometrial and Ovarian Cancers

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2024 Dec 25

PMID 39720923

Authors

M Zanjirband

M H Nasr-Esfahani

N J Curtin

Y Drew

S Sharma Saha

P Adibi

J Lunec

Affiliations

Soon will be listed here.

Abstract

Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA. This is achieved by conducting a thorough literature review and utilising specific search terms to identify all relevant studies published in English from 2010 to December 2022. PRISMA was followed, and the protocol was registered on PROSPERO (CRD42022375461). The QUADAS-2 tool and Review Manager Software were employed to evaluate study quality and risk of bias respectively. Forty-five eligible studies were selected with molecular signatures based on genomic, transcriptomic, metabolomic, proteomic and epigenetic analyses. Genes and their products deregulated in EC and/or OVCA were identified, including BRCA1, MLH1, NQO1 and ESR1, which were also deregulated in PCOS. Serum levels of IGF1, IGFBP1, SREBP1 and visfatin in women with PCOS were also identified as potential biomarkers of enhanced EC risk. Salusin-β serum levels in individuals with PCOS were identified as a potential biomarker for increased risk of OVCA. Gene signature-based drug repositioning identified several drug candidates: metformin, fenofibrate, fatostatin, melatonin, resveratrol and quercetin, some already established and prescribed for PCOS. In conclusion, this study provides a strong basis for further research to confirm the identified molecular signatures and associated causal links for potential therapeutic prevention strategies for EC and OVCA in women with PCOS.

References

Zhang Q, Chen W, Zhang X, Zhang H, Wang H, Zheng F . Overexpression of salusin-β is associated with poor prognosis in ovarian cancer. Oncol Rep. 2017; 37(3):1826-1832. DOI: 10.3892/or.2017.5429. View

Ramly B, Afiqah-Aleng N, Mohamed-Hussein Z . Protein-Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome. Int J Mol Sci. 2019; 20(12). PMC: 6627153. DOI: 10.3390/ijms20122959. View

Li L, Zhang J, Deng Q, Li J, Li Z, Xiao Y . Proteomic Profiling for Identification of Novel Biomarkers Differentially Expressed in Human Ovaries from Polycystic Ovary Syndrome Patients. PLoS One. 2016; 11(11):e0164538. PMC: 5112797. DOI: 10.1371/journal.pone.0164538. View

Xiong Y, Bian C, Lin X, Wang X, Xu K, Zhao X . Methylenetetrahydrofolate reductase gene polymorphisms in the risk of polycystic ovary syndrome and ovarian cancer. Biosci Rep. 2020; 40(7). PMC: 7369393. DOI: 10.1042/BSR20200995. View

Xia H, Zhao Y . miR-155 is high-expressed in polycystic ovarian syndrome and promotes cell proliferation and migration through targeting PDCD4 in KGN cells. Artif Cells Nanomed Biotechnol. 2019; 48(1):197-205. DOI: 10.1080/21691401.2019.1699826. View

Shafiee M, Ortori C, Barrett D, Mongan N, Abu J, Atiomo W . Lipidomic Biomarkers in Polycystic Ovary Syndrome and Endometrial Cancer. Int J Mol Sci. 2020; 21(13). PMC: 7370092. DOI: 10.3390/ijms21134753. View

Englert-Golon M, Andrusiewicz M, Zbikowska A, Chmielewska M, Sajdak S, Kotwicka M . Altered Expression of , , and Genes Is Associated with Ovarian Cancer Manifestation. Int J Mol Sci. 2021; 22(12). PMC: 8228770. DOI: 10.3390/ijms22126216. View

Wang Z, Li T, Zhang W, You L, Zhao Y, Xia M . Variants in DENND1A and LHCGR are associated with endometrioid adenocarcinoma. Gynecol Oncol. 2012; 127(2):403-5. DOI: 10.1016/j.ygyno.2012.08.007. View

Li W, Tai Y, Zhou J, Gu W, Bai Z, Zhou T . Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis. Cell Cycle. 2012; 11(12):2348-58. PMC: 3383594. DOI: 10.4161/cc.20811. View

10.

Shafiee M, Mongan N, Seedhouse C, Chapman C, Deen S, Abu J . Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer. Acta Obstet Gynecol Scand. 2017; 96(5):556-562. DOI: 10.1111/aogs.13106. View

11.

Xu X, Guan R, Gong K, Xie H, Shi L . Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome. Reprod Biol Endocrinol. 2022; 20(1):32. PMC: 8851856. DOI: 10.1186/s12958-022-00891-9. View

12.

Makrinou E, Drong A, Christopoulos G, Lerner A, Chapa-Chorda I, Karaderi T . Genome-wide methylation profiling in granulosa lutein cells of women with polycystic ovary syndrome (PCOS). Mol Cell Endocrinol. 2019; 500:110611. PMC: 7116598. DOI: 10.1016/j.mce.2019.110611. View

13.

Miao C, Chen Y, Fang X, Zhao Y, Wang R, Zhang Q . Identification of the shared gene signatures and pathways between polycystic ovary syndrome and endometrial cancer: An omics data based combined approach. PLoS One. 2022; 17(7):e0271380. PMC: 9278750. DOI: 10.1371/journal.pone.0271380. View

14.

Cirillo P, Wang E, Cedars M, Chen L, Cohn B . Irregular menses predicts ovarian cancer: Prospective evidence from the Child Health and Development Studies. Int J Cancer. 2016; 139(5):1009-17. PMC: 6917033. DOI: 10.1002/ijc.30144. View

15.

Siddamalla S, Reddy T, Govatati S, Guruvaiah P, Deenadayal M, Shivaji S . Influence of tumour suppressor gene (TP53, BRCA1 and BRCA2) polymorphisms on polycystic ovary syndrome in South Indian women. Eur J Obstet Gynecol Reprod Biol. 2018; 227:13-18. DOI: 10.1016/j.ejogrb.2018.05.027. View

16.

Paulson M, Norstedt G, Sahlin L, Linden Hirschberg A . Association between prolactin receptor expression and proliferation in the endometrium of obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2019; 36(3):226-232. DOI: 10.1080/09513590.2019.1650343. View

17.

Whiting P, Rutjes A, Westwood M, Mallett S, Deeks J, Reitsma J . QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011; 155(8):529-36. DOI: 10.7326/0003-4819-155-8-201110180-00009. View

18.

Desai A, Madar I, Asangani A, Al Ssadh H, Tayubi I . Influence of PCOS in Obese vs. Non-Obese women from Mesenchymal Progenitors Stem Cells and Other Endometrial Cells: An in silico biomarker discovery. Bioinformation. 2017; 13(4):111-115. PMC: 5429969. DOI: 10.6026/97320630013111. View

19.

Zanjirband M, Baharlooie M, Safaeinejad Z, Nasr-Esfahani M . Transcriptomic screening to identify hub genes and drug signatures for PCOS based on RNA-Seq data in granulosa cells. Comput Biol Med. 2023; 154:106601. DOI: 10.1016/j.compbiomed.2023.106601. View

20.

Jiao J, Sagnelli M, Shi B, Fang Y, Shen Z, Tang T . Genetic and epigenetic characteristics in ovarian tissues from polycystic ovary syndrome patients with irregular menstruation resemble those of ovarian cancer. BMC Endocr Disord. 2019; 19(1):30. PMC: 6416936. DOI: 10.1186/s12902-019-0356-5. View