循环肿瘤DNA甲基化状态在胃癌筛查和诊治中的研究进展  

Progress of circulating tumor DNA methylation for gastric cancer screening and management

作　　者：曹钦兴 严力 侯能易[1] 陈锦锋 余松 陆河江 旦真甲 庞明辉 Cao Qinxing;Yan Li;Hou Nengyi;Chen Jinfeng;Yu Song;Lu Hejiang;Dan Zhenjia;Pang Minghui(Department of Geriatric General Surgery,Sichuan Provincial People's Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,China)

机构地区：[1]四川省医学科学院·四川省人民医院(电子科技大学附属医院)老年综合外科,成都610072

出　　处：《中华胃肠外科杂志》2024年第5期535-544,共10页Chinese Journal of Gastrointestinal Surgery

基　　金：四川省科技厅重点研发项目(2022YFS0220);电子科技大学医工交叉联合基金(ZYGX2021YGLH212)。

摘　　要：循环肿瘤DNA是由肿瘤或循环肿瘤细胞释放的游离DNA,含有大量的肿瘤特征信息,这些特征可作为癌症早筛、监测、预后及预测治疗反应的生物标记物。目前还没有优质的筛查、监测及预测方法的胃癌领域极具吸引力。胃癌具有极大的肿瘤异质性,不同的胃癌亚组遗传特征和表观遗传特征差异性大,甲基化循环肿瘤DNA的敏感性和特异性高,有助于明确肿瘤基因分型,便于制定精确的诊治策略。此外,大量研究也证实了甲基化DNA在预测治疗反应、辅助治疗及耐药性评估上具有独特优势,在未来可以用于增强化疗方案的疗效和改善患者的化疗反应,甚至治疗多药耐药等。但甲基化循环肿瘤DNA也面临着诸多问题,如在单靶点的敏感性和特异性不高,部分胃癌亚型与循环肿瘤DNA关联有限、有脱靶风险、大样本及高质量临床研究证据缺乏等不足。本综述主要总结了目前对胃癌循环肿瘤DNA甲基化状态的研究,并将这些发现与胃癌早筛、复发监测和潜在的治疗机会联系起来,随着技术的进步和医工交叉研究的深入,循环肿瘤DNA检测将揭示更多疾病信息,成为胃癌领域和精准医学治疗的重要基础。Circulating tumor DNA(ctDNA)is cell-free DNA released by tumors or circulating tumor cells,containing abundant tumor-specific information that can serve as biomarkers for cancer early screening,monitoring,prognosis,and prediction of treatment response.This is particularly attractive in the field of gastric cancer,where high-quality screening,monitoring,and prediction methods are currently lacking.Gastric cancer exhibits significant tumor heterogeneity,with large differences in genetic and epigenetic characteristics among different subgroups.Methylated ctDNA has high sensitivity and specificity,which can help clarify tumor genotyping and facilitate the formulation of precise diagnostic and therapeutic strategies.Furthermore,numerous studies have confirmed the unique advantages of methylated DNA in predicting treatment response,adjuvant therapy,and drug resistance assessment,which may be used in the future to enhance the efficacy of chemotherapy regimens and improve patient chemotherapeutic response,and even treat multidrug resistance.However,there are several challenges associated with methylated ctDNA,such as low sensitivity and specificity at single-target sites,limited association between some gastric cancer subtypes and ctDNA,off-target risks,and the lack of large-scale and high-quality clinical research evidence.This review mainly summarizes current research on the methylation status of ctDNA in gastric cancer and connects these findings to early screening,recurrence monitoring,and potential treatment opportunities for gastric cancer.With advances in technology and the deepening of interdisciplinary research,ctDNA detection will reveal more disease information and become an essential foundation for gastric cancer research and precision medicine treatment.

关 键 词：胃肿瘤 DNA甲基化 循环肿瘤DNA 生物标志物 早期筛查 

分 类 号：R735.2[医药卫生—肿瘤]