子宫内膜增生的遗传标志物：从发病机制到个体化治疗

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子宫内膜增生，尤其在围绝经期，是妇科领域具有重要临床意义的问题之一，因为其向子宫内膜癌恶变的风险由基因异常与激素失衡之间的复杂相互作用共同决定。有观点认为，多种遗传标志物（ESR1、C-MYC、PIK3CA、PTENP1、MTHFR、EGFR）可能通过影响细胞增殖、凋亡以及 DNA 甲基化的调控而参与子宫内膜增生的发生机制。ESR1基因多态性可增加雌激素受体密度，从而增强子宫内膜的增殖反应。C-MYC的高表达与向不典型增生形式的进展呈相关性，但在生理性再生过程中同样可见。PIK3CA突变会造成PI3K/AKT/mTOR通路的持续激活，并与治疗抵抗有关。PTENP1假基因功能缺失破坏了对抑癌基因PTEN的调控，促进失控增殖。MTHFR多态性导致DNA甲基化受损，提高对表观遗传异常的易感性。EGFR过表达通过MAPK/ERK通路增强增殖效应，且在伴有肥胖的患者中更为常见。这些标志物的临床意义往往依赖于基础状态；由于人群差异及研究方法的异质性，其作用仍不完全明确。未来治疗的一个前景方向是建立整合性预测模型，将基因检测与临床参数相结合，用于风险分层及子宫内膜癌的早期预防。

作者简介

Alexey V. Overko

Pirogov Russian National Research Medical University

编辑信件的主要联系方式.
Email: leha.overko@yandex.ru
ORCID iD: 0000-0002-4629-9074
SPIN 代码: 5519-2836
俄罗斯联邦, Moscow

Tatiana F. Kovalenko

Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: t_kov@mail.ru
ORCID iD: 0000-0001-6091-892X
SPIN 代码: 6866-1360

Cand. Sci. (Biology)

俄罗斯联邦, Moscow

Lyudmila A. Ozolinya

Pirogov Russian National Research Medical University

Email: ozolinya@yandex.ru
ORCID iD: 0000-0002-2353-123X
SPIN 代码: 9407-9014

MD, Dr. Sci. (Medicine); Professor

俄罗斯联邦, Moscow

Svetlana A. Khlynova

Pirogov Russian National Research Medical University

Email: doc-khlinova@mail.ru
ORCID iD: 0000-0003-1554-3633
SPIN 代码: 7823-2660

MD, Cand. Sci. (Medicine); Assistant Professor

俄罗斯联邦, Moscow

Tatiana N. Savchenko

Pirogov Russian National Research Medical University

Email: 12111944t@mail.ru
ORCID iD: 0000-0001-7244-4944
SPIN 代码: 3157-3682

MD, Dr. Sci. (Medicine), Professor

俄罗斯联邦, Moscow

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