DNA甲基化检测助力肿瘤早期筛查和诊断

DNA methylation detection assists early screening and diagnosis of tumors

DNA甲基化是国内外癌症早筛采用的常用检测指标。在致癌因素的作用下,抑癌基因启动子区的高甲基化可导致基因表达下调或关闭,从而激活原癌基因的表达,促使肿瘤发生。用于DNA甲基化检测的样本主要采用脱落细胞、血液样本和石蜡包埋组织。常用的检测方法包括特异性聚合酶链反应(methylation-specific polymerase chain reaction,MSP)、核酸质谱、甲基化芯片、亚硫酸氢盐测序、第二代测序技术等。与突变检测相比,DNA甲基化的检测优势在于其肿瘤特异性高、可检测位点多、信号丰度高,且可实现组织溯源。目前,DNA甲基化检测被主要运用在临床脑胶质瘤用药指导、肺癌辅助诊断和高危分流、膀胱癌高危分流和复发监测、宫颈癌高危分流、结直肠癌和胃癌早期筛查及复发监测。在实现大规模临床常规应用前,需注意精准定位DNA甲基化检测的应用场景,相对于耐受性良好的内镜检查,其高危分流的刚需性可能会下降。在辅助诊断病理诊断灵敏度较低的肿瘤、肿瘤监测和预后评估方面,DNA甲基化检测有着重要的作用。随着检测流程和质量管理的规范,DNA甲基化检测会被更广泛地运用于临床,提高肿瘤的早筛和诊断灵敏度。

DNA methylation is one of the most widely used indicator for early cancer screening.Under the influence of carcinogens,hypermethylation of the promoter region of tumor suppressor genes may lead to downregulation or silencing of gene expression,thereby activating the expression of proto-oncogenes and promoting tumorigenesis.The samples used for DNA methylation detection are mainly exfoliated cells,blood samples and paraffin-embedded tissues.Commonly used detection methods include:methylation-specific polymerase chain reaction(MSP),nucleic acid mass spectrometry,methylation chip,bisulfite sequencing,next-generation sequencing,etc.Compared with mutation detection,the advantages of DNA methylation detection are that it has higher tumor specificity,more detectable sites,higher signal quality,and can achieve tissue traceability.Currently,it is mainly used clinically for medication guidance for brain glioma,aid in diagnosis and highrisk triage for lung cancer,high-risk triage and recurrence monitoring for bladder cancer,high-risk triage for cervical cancer,and early screening and recurrence monitoring for colorectal cancer and gastric cancer.Before large-scale clinical routine application,accurately positioning of the application scenarios for DNA methylation detection must be considered.For well-tolerated endoscopy,the rigid need of DNA methylation detection for high-risk triage may be reduced.DNA methylation detection plays an important role in assisting in the diagnosis of tumors with low pathological diagnosis sensitivity,tumor monitoring and prognosis assessment.With the standardization of testing procedures and quality management,DNA methylation detection will be more widely used to improve the early screening and diagnostic sensitivity of tumors.