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子宫平滑肌瘤中氧化应激相关生物标志物的鉴定:转录组联合孟德尔随机化分析

Identification of oxidative stress-related biomarkers in uterine leiomyoma: a transcriptome-combined Mendelian randomization analysis.

作者信息

Li Yingxiao, Chen Haoyue, Zhang Hao, Lin Zhaochen, Song Liang, Zhao Chuanliang

机构信息

Department of Gynecology, The Affiliated Taian City Central Hospital of Qingdao University, Tai'an, Shandong, China.

Department of Rehabilitation Medical Center, The Affiliated Taian City Central Hospital of Qingdao University, Tai'an, Shandong, China.

出版信息

Front Endocrinol (Lausanne). 2024 Nov 21;15:1373011. doi: 10.3389/fendo.2024.1373011. eCollection 2024.

Abstract

BACKGROUND

Oxidative stress has been implicated in the pathogenesis of uterine leiomyoma (ULM) with an increasing incidence. This study aimed to identify potential oxidative stress-related biomarkers in ULM using transcriptome data integrated with Mendelian randomization (MR) analysis.

METHODS

Data from GSE64763 and GSE31699 in the Gene Expression Omnibus (GEO) were included in the analysis. Oxidative stress-related genes (OSRGs) were identified, and the intersection of differentially expressed genes (DEGs), Weighted Gene Co-expression Network Analysis (WGCNA) genes, and OSRGs was used to derive differentially expressed oxidative stress-related genes (DE-OSRGs). Biomarkers were subsequently identified MR analysis, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. Nomograms, regulatory networks, and gene-drug interaction networks were constructed based on the identified biomarkers.

RESULTS

A total of 883 DEGs were identified between ULM and control samples, from which 42 DE-OSRGs were screened. MR analysis revealed four biomarkers: , , , and . Predictive nomograms were generated based on these biomarkers. , , and were significantly enriched in chemokine signaling and other pathways. Notably, showed strong associations with follicular helper T cells, resting mast cells, and M0 macrophages. was positively correlated with resting mast cells, while was negatively correlated with macrophages. Additionally, displayed strong binding energy with amcinonide, and with ribavirin.

CONCLUSION

This study identified oxidative stress-related biomarkers (ANXA1, CD36, MICB, and PRDX6) in ULM through transcriptomic and MR analysis, providing valuable insights for ULM therapeutic research.

摘要

背景

氧化应激与发病率不断上升的子宫平滑肌瘤(ULM)的发病机制有关。本研究旨在利用转录组数据结合孟德尔随机化(MR)分析来识别ULM中潜在的氧化应激相关生物标志物。

方法

分析纳入了基因表达综合数据库(GEO)中的GSE64763和GSE31699数据。识别氧化应激相关基因(OSRGs),并利用差异表达基因(DEGs)、加权基因共表达网络分析(WGCNA)基因和OSRGs的交集来推导差异表达的氧化应激相关基因(DE-OSRGs)。随后通过MR分析识别生物标志物,接着进行基因集富集分析(GSEA)和免疫浸润分析。基于识别出的生物标志物构建列线图、调控网络和基因-药物相互作用网络。

结果

在ULM和对照样本之间共识别出883个DEGs,从中筛选出42个DE-OSRGs。MR分析揭示了四个生物标志物: 、 、 和 。基于这些生物标志物生成了预测列线图。 、 和 在趋化因子信号传导和其他途径中显著富集。值得注意的是, 与滤泡辅助性T细胞、静息肥大细胞和M0巨噬细胞显示出强烈关联。 与静息肥大细胞呈正相关,而 与巨噬细胞呈负相关。此外, 与安西奈德显示出强结合能, 与利巴韦林显示出强结合能。

结论

本研究通过转录组学和MR分析在ULM中识别出氧化应激相关生物标志物(膜联蛋白A1、CD36、MICA/B和PRDX6),为ULM治疗研究提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daf5/11617171/c8db121991c8/fendo-15-1373011-g001.jpg

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