The Role of Somatic Mutations in Endometriosis: Pathogenesis, Progression and Fibrogenesis (Systematic Review)

IF 3.3 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Journal of minimally invasive gynecology Pub Date : 2025-10-22 DOI:10.1016/j.jmig.2025.09.029

LV Adamyan , L Pivazyan , AA Stepanian , M Yurkanova , E Zarova , M Knuznetsova , K Mailova , D Trofimov

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引用次数: 0

Abstract

Study Objective

To systematically review and analyze the role of somatic mutations in the pathogenesis of endometriosis, their association with fibrogenesis, and their potential as diagnostic biomarkers and therapeutic targets.

Design

Systematic review of original research articles and systematic reviews published up to January 7, 2025, following PRISMA guidelines.

Setting

Laboratory-based genomic studies analyzing patient-derived endometriotic tissue samples, primarily formalin-fixed, paraffin-embedded specimens, using high-sensitivity next-generation sequencing (NGS) and laser-capture microdissection (LCM) techniques to enrich epithelial components.

Patients or Participants

742 women with confirmed endometriosis and 410 control subjects (ages 21–56), from studies evaluating somatic mutations across various morphologic subtypes of endometriosis including ovarian endometriomas, deep infiltrating endometriosis, and superficial peritoneal lesions.

Interventions

Not applicable (systematic review of genomic studies).

Measurements and Primary Results

Primary outcomes included the identification and characterization of somatic mutations and their correlation with fibrogenesis and oxidative stress markers. Frequent mutations were found in oncogenic and tumor suppressor genes such as ARID1A, PIK3CA, KRAS, and PTEN. These mutations were enriched in the epithelial component of lesions and correlated with enhanced fibrogenic signaling pathways, including PI3K/AKT and TGF-β. Evidence suggests a contribution of oxidative stress to mutagenesis, promoting lesion persistence and fibrosis.

Conclusion

Somatic mutations may contribute to the pathogenesis and fibrogenesis of endometriosis and could serve as biomarkers for diagnosis, classification, and targeted therapy development. However, a definitive cause-effect relationship remains to be clarified. Future longitudinal studies integrating genomic and epigenomic analyses are essential to translate these findings into clinical practice and precision medicine approaches.

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体细胞突变在子宫内膜异位症中的作用：发病、进展和纤维化（系统综述）

研究目的系统回顾和分析体细胞突变在子宫内膜异位症发病机制中的作用、与纤维发生的关系及其作为诊断生物标志物和治疗靶点的潜力。按照PRISMA指南，对2025年1月7日前发表的原创研究文章和系统综述进行系统综述。基于实验室的基因组研究分析了患者来源的子宫内膜异位症组织样本，主要是福尔马林固定，石蜡包埋的样本，使用高灵敏度下一代测序（NGS）和激光捕获显微解剖（LCM）技术来丰富上皮成分。患者或参与者：742名确诊子宫内膜异位症的女性和410名对照受试者（年龄21-56岁），来自评估子宫内膜异位症各种形态亚型（包括卵巢子宫内膜异位症、深部浸润性子宫内膜异位症和浅表腹膜病变）的体细胞突变的研究。干预措施：不适用（基因组研究的系统回顾）。测量和主要结果主要结果包括体细胞突变的鉴定和表征及其与纤维发生和氧化应激标志物的相关性。在致癌和肿瘤抑制基因如ARID1A、PIK3CA、KRAS和PTEN中发现了频繁的突变。这些突变在病变的上皮成分中富集，并与增强的纤维化信号通路相关，包括PI3K/AKT和TGF-β。有证据表明氧化应激有助于突变，促进病变持续和纤维化。结论体细胞突变可能参与子宫内膜异位症的发病机制和纤维化过程，可作为诊断、分类和制定靶向治疗方案的生物标志物。然而，明确的因果关系仍有待澄清。整合基因组和表观基因组分析的未来纵向研究对于将这些发现转化为临床实践和精准医学方法至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of minimally invasive gynecology 医学-妇产科学

CiteScore

5.00

自引率

7.30%

发文量

272

审稿时长

37 days

期刊介绍： The Journal of Minimally Invasive Gynecology, formerly titled The Journal of the American Association of Gynecologic Laparoscopists, is an international clinical forum for the exchange and dissemination of ideas, findings and techniques relevant to gynecologic endoscopy and other minimally invasive procedures. The Journal, which presents research, clinical opinions and case reports from the brightest minds in gynecologic surgery, is an authoritative source informing practicing physicians of the latest, cutting-edge developments occurring in this emerging field.