Muresu Narcisa, Puci Mariangela Valentina, Sotgiu Giovanni, Sechi Illari, Cossu Andrea, Usai Manuela, Piana Andrea Fausto
Medical Management, Hygiene, Epidemiology and Hospital Infection, University Hospital of Sassari, 07100 Sassari, Italy.
Clinical Epidemiology and Medical Statistics Unit, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy.
Healthcare (Basel). 2024 Sep 30;12(19):1951. doi: 10.3390/healthcare12191951.
DNA methylation-based biomarkers have been investigated as useful tools in the carcinogenesis process, including the triage of HPV-associated cancers. In this context, we conducted a systematic review and meta-analysis focused on evaluating the changes in the level of DNA methylation in cases of pre-cancerous (i.e., anal intraepithelial neoplasia, AIN-1, -2., -3) and cancerous (i.e., squamous cell carcinoma, SCC) anal lesions.
A research in the PubMed, Scopus, and Web of Science databases was carried out, following the PRISMA 2020 protocol, using the following keywords: "anal cancer", "anal intraepithelial neoplasia", "methylation", and "epigenetic". All observational studies that reported the level of DNA methylation by grade of anal lesions and for different target genes were included. The QUADAS-2 tool was used to assess the studies' quality, whereas pooled prevalence, sensitivity, specificity, and diagnostic odds ratio (DOR) were employed to verify the accuracy of the test in the detection of high-grade lesions.
Eight studies met the inclusion criteria, involving a total of 1555 clinical samples. The prevalence of methylation-positive samples by histological grading was 27%, 45%, 54%, and 98% for AIN1, AIN2, AIN3, and SCC, respectively. Similar results were observed for the DOR, with higher ORs in more severe lesions. The pooled AUC (95%CI) for the diagnosis of ≥AIN2 was 0.68 (0.63-0.73).
The present review and meta-analysis support the introduction of DNA methylation-based biomarkers in the triage of subjects with low-grade anal lesions and in the monitoring of treatment outcomes. Standardized protocols and a prospective study design are needed to implement methylation tests in clinical practice.
基于DNA甲基化的生物标志物已被研究作为癌症发生过程中的有用工具，包括人乳头瘤病毒相关癌症的分类。在此背景下，我们进行了一项系统综述和荟萃分析，重点评估癌前病变（即肛管上皮内瘤变，AIN-1、-2、-3）和癌性病变（即鳞状细胞癌，SCC）病例中DNA甲基化水平的变化。
按照PRISMA 2020方案，在PubMed、Scopus和Web of Science数据库中进行检索，使用以下关键词：“肛管癌”、“肛管上皮内瘤变”、“甲基化”和“表观遗传学”。纳入所有报告了按肛管病变分级和不同靶基因的DNA甲基化水平的观察性研究。使用QUADAS-2工具评估研究质量，而汇总患病率、敏感性、特异性和诊断比值比（DOR）用于验证检测高级别病变时检测方法的准确性。
八项研究符合纳入标准，共涉及1555份临床样本。按组织学分级，AIN1、AIN2、AIN3和SCC的甲基化阳性样本患病率分别为27%、45%、54%和98%。DOR也观察到类似结果，病变越严重OR值越高。诊断≥AIN2的汇总AUC（95%CI）为0.68（0.63-0.73）。
本综述和荟萃分析支持在低级别肛管病变患者的分类以及治疗结果监测中引入基于DNA甲基化的生物标志物。在临床实践中实施甲基化检测需要标准化方案和前瞻性研究设计。
