Tepus Melanie, Yau Tung On
John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Gastrointest Tumors. 2020 Jul;7(3):62-73. doi: 10.1159/000507701. Epub 2020 May 20.
Colorectal cancer (CRC) follows a protracted stepwise progression, from benign adenomas to malignant adenocarcinomas. If detected early, 90% of deaths are preventable. However, CRC is asymptomatic in its early-stage and arises sporadically within the population. Therefore, CRC screening is a public health priority.
Faecal immunochemical test (FIT) is gradually replacing guaiac faecal occult blood test and is now the most commonly used screening tool for CRC screening program globally. However, FIT is still limited by the haemoglobin degradation and the intermittent bleeding patterns, so that one in four CRC cases are still diagnosed in a late stage, leading to poor prognosis. A multi-target stool DNA test (Cologuard, a combination of and DNA methylation, mutations, and haemoglobin) and a plasma DNA methylation test (Epi proColon) are non-invasive tools also approved by the US FDA, but those screening approaches are not cost-effective, and the detection accuracies remain unsatisfactory. In addition to the approved tests, faecal-/blood-based microRNA and CRC-related gut microbiome screening markers are under development, with work ongoing to find the best combination of molecular biomarkers which maximise the screening sensitivity and specificity.
Maximising the detection accuracy with a cost-effective approach for non-invasive CRC screening is urgently needed to further reduce the incidence of CRC and associated mortality rates.
结直肠癌(CRC)遵循从良性腺瘤到恶性腺癌的漫长逐步进展过程。如果早期发现,90%的死亡是可预防的。然而,CRC在早期无症状,且在人群中散发出现。因此,CRC筛查是公共卫生的重点。
粪便免疫化学检测(FIT)正在逐渐取代愈创木脂粪便潜血检测,现在是全球CRC筛查项目中最常用的筛查工具。然而,FIT仍受血红蛋白降解和间歇性出血模式的限制,以至于四分之一的CRC病例仍在晚期被诊断出来,导致预后不良。多靶点粪便DNA检测(Cologuard,一种结合了 和 DNA甲基化、 突变以及血红蛋白的检测方法)和血浆 DNA甲基化检测(Epi proColon)也是经美国食品药品监督管理局(FDA)批准的非侵入性工具,但这些筛查方法不具有成本效益,且检测准确性仍不令人满意。除了已批准的检测方法外,基于粪便/血液的微小RNA和与CRC相关的肠道微生物组筛查标志物正在研发中,目前正在努力寻找能使筛查敏感性和特异性最大化的分子生物标志物的最佳组合。
迫切需要采用具有成本效益的方法来最大限度地提高非侵入性CRC筛查的检测准确性,以进一步降低CRC的发病率和相关死亡率。