Spatiotemporal Evolutionary Mechanisms and Translational Research Progress in the Malignant Transformation of Endometriosis: A Comprehensive Review

子宫内膜异位症恶变转化的时空演变机制及其转化医学研究进展 Spatiotemporal Evolutionary Mechanisms and Translational Research Progress in the Malignant Transformation of Endometriosis: A Comprehensive Review Spatiotemporal Evolutionary Mechanisms and Translational Research Progress in the Malignant Transformation of Endometriosis: A Comprehensive Review DOI: 10.12677/jcpm.2026.52170, PDF, 被引量 作者: 刘少璇, 赵蓉蓉, 陈 佳：延安大学延安医学院，陕西 延安；贺 晶*：延安大学附属医院妇科，陕西 延安 关键词: 子宫内膜异位症；卵巢透明细胞癌；子宫内膜样癌；铁过载；空间转录组学；合成致死；肿瘤微环境；Endometriosis； Ovarian Clear Cell Carcinoma； Endometrioid Ovarian Carcinoma； Spatiotemporal Evolution； Iron Overload； ARID1A Mutation； Spatial Transcriptomics； Synthetic Lethality； Tumor Microenvironment 作者: 刘少璇, 赵蓉蓉, 陈 佳：延安大学延安医学院，陕西 延安；贺 晶*：延安大学附属医院妇科，陕西 延安 关键词: 子宫内膜异位症；卵巢透明细胞癌；子宫内膜样癌；铁过载；空间转录组学；合成致死；肿瘤微环境；Endometriosis； Ovarian Clear Cell Carcinoma； Endometrioid Ovarian Carcinoma； Spatiotemporal Evolution； Iron Overload； ARID1A Mutation； Spatial Transcriptomics； Synthetic Lethality； Tumor Microenvironment 摘要: 背景与目的：子宫内膜异位症和特定亚型卵巢癌，即透明细胞癌与子宫内膜样癌(统称EAOC)，二者存在恶性转化的关联，此为妇科肿瘤学中的核心议题之一。本文的目的在于对EAOC的流行病学特征进行系统梳理，并从多维度重新构建一个从良性异位病灶向恶性肿瘤演进的“时空连续体”病理模型。核心内容：该综述细致探究了不同高危表型的微环境演进差异：深部浸润型病灶(DIE)的致密纤维化与缺氧驱动了代谢重编程，而卵巢囊肿封闭微环境里的铁过载(Iron overload)机制，则清晰解释了芬顿(Fenton)反应引发的强氧化应激如何促使持续的DNA损伤以及脂质过氧化。在这样的组织微环境中，以ARID1A基因突变作为关键的隐匿性基因组崩溃，比组织学方面的非典型性变化出现得早许多。结合病灶局部出现的内分泌重编程情况，其中包含芳香化酶异常高表达以及孕激素抵抗的情况，突变克隆因而获得不可逆的增殖优势。此外，借助最新的空间转录组学以及单细胞测序所提供的证据，本文展现出一个由癌症相关成纤维细胞(CAFs)形成的物理屏障、巨噬细胞的极化情况以及补体系统的劫持状况共同交织而成的免疫逃逸网络。临床转化与展望：借助多组学机制，本文全面评测液体活检在早期监测方面的潜力，精准分子分型所推动的靶向“合成致死”策略(比如EZH2/ATR抑制剂)以及特异性瓦解CAF与细胞外基质物理屏障的微环境重塑疗法在真实世界中的临床进展状况，其目的在于为涵盖全生命周期的高危人群精准管理以及降期治疗提供具有前瞻性的转化医学指导。 Abstract: Objective: The oncogenic link between endometriosis and specific ovarian cancer subtypes (clear cell and endometrioid carcinomas, collectively termed EAOC) remains a pivotal challenge in clinical management. This review aims to transcend the limitations of traditional morphological descriptions, reconstructing a “spatiotemporal continuum” model of EAOC pathogenesis through the lenses of microenvironmental constraints, molecular evolution, and translational medicine. Mechanisms: We systematically dissect the divergent microenvironmental drivers of high-risk phenotypes: the dense fibrosis and hypoxia in deep infiltrating endometriosis (DIE) that promote metabolic reprogramming, versus the iron overload effects within the enclosed microenvironment of endometriomas, detailing how Fenton reaction-induced oxidative stress drives continuous DNA damage and lipid peroxidation. Building upon this, the review focuses on the synergistic carcinogenic roles of early ARID1A mutation-triggered genomic crash—which precedes atypical histological changes—and local endocrine reprogramming (aromatase overexpression and progesterone resistance), granting mutant clones an irreversible proliferative advantage. Integrating recent spatial transcriptomics and single-cell sequencing evidence, we further unveil an immunosuppressive network orchestrated by the physical barriers of cancer-associated fibroblasts (CAFs), macrophage polarization, and the hijacking of the complement system. Clinical Translation: Anchored in these mechanisms, we evaluate the performance of “synthetic lethality” strategies (e.g., EZH2/ATR inhibitors) in real-world clinical trials for ARID1A-deficient EAOC, alongside emerging microenvironment-remodeling therapies aimed at dismantling the CAF-mediated physical barriers. 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