UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
UCD Clinical Research Centre, St. Vincent's University Hospital, Dublin, Ireland.
Clin Chem Lab Med. 2021 Apr 15;59(8):1353-1361. doi: 10.1515/cclm-2021-0171. Print 2021 Jul 27.
The detection of cancer at an early stage while it is curable by surgical resection is widely believed to be one of the most effective strategies for reducing cancer mortality. Hence, the intense interests in the development of a simple pan-cancer screening test. Lack of sensitivity and specificity when combined with the low prevalence of most types of cancer types in the general population limit the use of most of the existing protein biomarkers for this purpose. Like proteins, tumor DNA also can be released into the circulation. Such circulating tumor DNA (ctDNA) can be differentiated from normal cell DNA by the presence of specific genetic alteration such as mutations, copy number changes, altered methylation patterns or being present in different sized fragments. Emerging results with test such as CancerSEEK or GRAIL suggest that the use of ctDNA can detect cancer with specificities >99%. Sensitivity however, is cancer type and stage-dependent, varying from approximately 40% in stage I disease to approximately 80% in stage III disease. It is important to stress however, that most of the studies published to date have used patients with an established diagnosis of cancer while the control population were healthy individuals. Although the emerging results are promising, evidence of clinical utility will require demonstration of reduced mortality following evaluation in a prospective randomized screening trial.
早期癌症的检测，在可通过手术切除时进行治疗，被广泛认为是降低癌症死亡率的最有效策略之一。因此，人们强烈关注开发一种简单的泛癌筛查测试。由于与大多数常见人群中的癌症类型的低患病率相结合的敏感性和特异性不足，大多数现有的蛋白质生物标志物在这方面的应用受到限制。与蛋白质一样，肿瘤 DNA 也可以释放到循环中。通过存在特定的遗传改变（如突变、拷贝数变化、改变的甲基化模式或存在不同大小的片段），可以将这种循环肿瘤 DNA（ctDNA）与正常细胞 DNA 区分开来。像 CancerSEEK 或 GRAIL 这样的检测方法的新结果表明，ctDNA 的使用可以特异性 >99%地检测癌症。然而，敏感性取决于癌症类型和分期，从 I 期疾病的约 40%到 III 期疾病的约 80%不等。然而，重要的是要强调，迄今为止发表的大多数研究都使用了已经确诊患有癌症的患者，而对照组是健康个体。尽管新出现的结果很有希望，但在前瞻性随机筛查试验中评估后的临床实用性证据将需要证明死亡率降低。
