ASTN1、DLX1、ITGA4、RXFP3、SOX17和ZNF671六基因甲基化在宫颈癌及 宫颈癌前病变中的研究进展

Research Progress on the Methylation of the Six Genes ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671 in Cervical Cancer and Cervical Precancerous Lesions

摘要: 宫颈癌是女性生殖系统常见恶性肿瘤，其发生发展与高危型人乳头瘤病毒(high-risk human papillomavirus, hrHPV)持续感染密切相关。近年来，随着宫颈癌筛查的普及，如何在保证筛查敏感性的同时提高对高级别病变的识别能力、降低不必要的阴道镜转诊率，成为宫颈癌防治领域的重要问题。DNA甲基化作为表观遗传调控的重要形式，在宫颈癌及宫颈癌前病变的发生、发展中发挥重要作用。与单基因甲基化检测相比，多基因联合甲基化检测能够更全面地反映宿主表观遗传异常，提高病变分层识别能力。ASTN1、DLX1、ITGA4、RXFP3、SOX17和ZNF671这六个基因构成的甲基化检测组合，是近年来较受关注的一类宿主甲基化标志物，在宫颈癌及宫颈癌前病变的筛查、hrHPV阳性人群的分流管理、病变风险评估以及辅助临床决策等方面，都显示出了较好的应用前景。本文就该六基因甲基化组合在宫颈癌及宫颈癌前病变中的生物学基础、临床应用价值、联合检测优势及存在问题进行综述，以期为宫颈癌精准筛查和个体化管理提供参考。

Abstract: Cervical cancer is a common malignancy of the female reproductive system, and its occurrence and progression are closely associated with persistent infection of high-risk human papillomavirus (hrHPV). In recent years, with the widespread implementation of cervical cancer screening, improving the ability to identify high-grade lesions while maintaining screening sensitivity and reducing unnecessary colposcopy referrals has become a critical issue in the field of cervical cancer prevention and control. As an important form of epigenetic regulation, DNA methylation plays a significant role in the development and progression of cervical cancer and cervical precancerous lesions. Compared with single-gene methylation detection, combined multi-gene methylation testing provides a more comprehensive reflection of host epigenetic abnormalities and enhances lesion stratification. The methylation detection panel consisting of the six genes—ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671, is a host methylation biomarker that has garnered considerable attention in recent years. It has shown promising application value in the screening of cervical cancer and precancerous lesions, triage management of hrHPV-positive populations, lesion risk assessment, and auxiliary clinical decision-making. This article reviews the biological basis, clinical application value, advantages of combined detection, and existing challenges of this six-gene methylation panel in cervical cancer and cervical precancerous lesions, aiming to provide a reference for precision screening and individualized management of cervical cancer.