Zanjirband M, Nasr-Esfahani M H, Curtin N J, Drew Y, Sharma Saha S, Adibi P, Lunec J
Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Translational and Clinical Research Institute, Newcastle University Cancer Centre, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
J Cell Mol Med. 2024 Dec;28(24):e70312. doi: 10.1111/jcmm.70312.
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.
多囊卵巢综合征（PCOS）是女性不孕的主要原因，影响4%-20%的育龄妇女。代谢和激素改变是PCOS的关键特征，可能增加子宫内膜癌（EC）和卵巢癌（OVCA）的风险。本系统评价旨在总结PCOS与EC或OVCA之间关联所涉及的分子机制。这是通过全面的文献综述并使用特定检索词来识别2010年至2022年12月以英文发表的所有相关研究来实现的。遵循PRISMA原则，并在PROSPERO（CRD42022375461）上注册了方案。分别使用QUADAS-2工具和Review Manager软件来评估研究质量和偏倚风险。基于基因组、转录组、代谢组、蛋白质组和表观遗传学分析，选择了45项具有分子特征的合格研究。确定了在EC和/或OVCA中失调的基因及其产物，包括BRCA1、MLH1、NQO1和ESR1，这些基因在PCOS中也失调。PCOS女性血清中IGF1、IGFBP1、SREBP-1和内脂素水平也被确定为EC风险增加的潜在生物标志物。PCOS患者血清中Salusin-β水平被确定为OVCA风险增加的潜在生物标志物。基于基因特征的药物重新定位确定了几种候选药物：二甲双胍、非诺贝特、脂肪抑制素、褪黑素、白藜芦醇和槲皮素，其中一些已被确立并用于治疗PCOS。总之，本研究为进一步研究提供了有力基础，以确认所确定的分子特征以及PCOS女性EC和OVCA潜在治疗预防策略的相关因果联系。
