Data_Sheet_3_Skeletal Muscle Immunometabolism in Women With Polycystic Ovary Syndrome: A Meta-Analysis.PDF

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting up to 15% of women at reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including hyperinsulinemia and insulin resistance and a 4-fold increased risk of developing type 2 diabetes. Despite the high prevalence the pathophysiology of the syndrome is unclear. Insulin resistance in women with PCOS likely affect the skeletal muscle and recently it was demonstrated that changes in DNA methylation affects the gene expression in skeletal muscle that in part can explain their metabolic abnormalities. The objective of this work was to combine gene expression array data from different datasets to improve statistical power and thereby identify novel biomarkers that can be further explored. In this narrative review, we performed a meta-analysis of skeletal muscle arrays available from Gene Expression Omnibus and from publications. The eligibility criteria were published articles in English, and baseline (no treatment) skeletal muscle samples from women with PCOS and controls. The R package Metafor was used for integration of the datasets. One hundred and fourteen unique transcripts were differentially expressed in skeletal muscle from women with PCOS vs. controls (q < 0.05), 87% of these transcripts have not been previously identified as altered in PCOS muscle. ING2, CDKAL1, and AKTIP had the largest differential increase in expression, and TSHZ2, FKBP2, and OCEL1 had the largest decrease in expression. Two genes, IRX3 and CDKAL1 were consistently upregulated (q < 0.05) in the individual analyses and meta-analysis. Based on the meta-analysis, we identified several dysregulated immunometabolic pathways as a part of the molecular mechanisms of insulin resistance in the skeletal muscle of women with PCOS. The transcriptomic data need to be verified by functional analyses as well as proteomics to advance our understanding of PCOS specific insulin resistance in skeletal muscle.

多囊卵巢综合征（PCOS）是一种内分泌和代谢性疾病，影响育龄女性中的高达15%。PCOS的主要特征为高睾酮血症、月经周期不规则以及代谢功能障碍，包括高胰岛素血症、胰岛素抵抗，以及2型糖尿病发病风险增加4倍。尽管该病的患病率较高，但其病理生理学尚不明确。PCOS女性中的胰岛素抵抗可能影响骨骼肌，近期研究表明，DNA甲基化的改变会影响骨骼肌的基因表达，部分解释了其代谢异常。本研究的目的是结合来自不同数据集的基因表达谱数据，以提高统计功效，从而识别出可进一步研究的新的生物标志物。在本篇综述中，我们对来自Gene Expression Omnibus和出版物中的骨骼肌阵列进行了荟萃分析。纳入标准为英文发表的已发表文章，以及PCOS女性和对照组的基线（未治疗）骨骼肌样本。使用R语言的Metafor包进行数据集的整合。在PCOS女性与对照组的骨骼肌中，有114个独特的转录本表达存在差异（q < 0.05），其中87%的转录本之前未被识别为在PCOS肌肉中发生改变。ING2、CDKAL1和AKTIP的表达差异最大，而TSHZ2、FKBP2和OCEL1的表达下降最大。在个体分析和荟萃分析中，IRX3和CDKAL1两种基因的表达持续上调（q < 0.05）。基于荟萃分析，我们确定了几个失调的免疫代谢通路，这些通路是PCOS女性骨骼肌胰岛素抵抗的分子机制的一部分。转录组数据需要通过功能分析和蛋白质组学进行验证，以深化我们对PCOS特异性骨骼肌胰岛素抵抗的理解。