关键词: Diagnosis Endoplasmic reticulum Nomogram Polycystic ovary syndrome

来  源:   DOI:10.1007/s43032-024-01619-3

Abstract:
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in premenopausal women. This investigation was to elucidate the underlying mechanism of endoplasmic reticulum stress (ERS) activation in granulosa cells, which has been implicated in the etiology of PCOS. Differentially expressed genes (DEGs) between PCOS and control groups were integrated with ERS gene lists from databases to identify DE-ERS genes, and functional analyses were performed. Univariate regression analysis and the LASSO method were used to select diagnostic factors, followed by establishing a DE-ERS gene-based diagnostic model. A nomogram model was further generated to predict the risk of PCOS. The correlation between ERS gene expression and immune cell proportion was assessed. A total of 14 DE-ERS genes associated with \"protein processing in endoplasmic reticulum\", \"ferroptosis\", and \"glycerophospholipid metabolism\" were selected as PCOS-related factors. An eight-DE-ERS genes-based diagnostic model was developed and displayed satisfactory performance in the training (Area under curve (AUC) = 0.983) and validation datasets (AUC = 0.802). High risk of PCOS can be accurately predicted, which might contribute to clinical decision-making. Moreover, EDEM1 expression was significantly positively correlated with naive B cell infiltration, while PDIA6 was negatively correlated with neutrophil proportion (P < 0.001). We identified eight novel molecules and developed an ERS gene-based diagnostic model in PCOS, which might provide novel insight for finding biomarkers and treatment methods.
摘要:
多囊卵巢综合征(PCOS)是绝经前妇女普遍存在的内分泌和代谢紊乱。这项研究是为了阐明颗粒细胞内质网应激(ERS)激活的潜在机制,这与PCOS的病因有关。PCOS和对照组之间的差异表达基因(DEGs)与数据库中的ERS基因列表整合,以鉴定DE-ERS基因。并进行功能分析。单因素回归分析和LASSO方法选择诊断因素,建立基于DE-ERS基因的诊断模型。进一步生成列线图模型来预测PCOS的风险。评估ERS基因表达与免疫细胞比例之间的相关性。共有14个与“内质网蛋白质加工”相关的DE-ERS基因,\"铁性凋亡\",选择“甘油磷脂代谢”作为PCOS相关因素。开发了基于8-DE-ERS基因的诊断模型,并在训练(曲线下面积(AUC)=0.983)和验证数据集(AUC=0.802)中显示出令人满意的性能。可以准确预测PCOS的高风险,这可能有助于临床决策。此外,EDEM1表达与幼稚B细胞浸润呈显著正相关,PDIA6与中性粒细胞比例呈负相关(P<0.001)。我们鉴定了8种新的分子,并开发了一种基于ERS基因的PCOS诊断模型。这可能为寻找生物标志物和治疗方法提供新的见解。
公众号