Vatandoost Nasimeh, Ghanbari Jahanafrooz, Mojaver Mahboobeh, Avan Amir, Ghayour-Mobarhan Majid, Nedaeinia Reza, Salehi Rasoul
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cancer Res Clin Oncol. 2016 Feb;142(2):341-51. doi: 10.1007/s00432-015-1928-z. Epub 2015 Feb 17.
Colorectal cancer (CRC) is one of the major health problems worldwide and is often diagnosed at late stage. There is growing body of evidence in early detection of this disease with novel screening modalities to reduce compliance and increase specificity of available methods. The aim of current review is to give an overview on currently available screening methods (e.g., fecal occult blood testing (FOBT), flexible sigmoidoscopy, and colonoscopy), with their own merits and disadvantages, and new genetic/epigenetic/protein markers, as novel screening modalities.
There are several serum and fecal biomarkers that can predict CRC and polyps. Overall sensitivities for detection by fecal DNA markers ranged from 53 to 87%, while a panel of serum protein markers provides a sensitivity/specificity up to 85% for CRC. In particular, DNA methylation markers (e.g., SEPT9, SFRP2, and ALX4), circulating microRNAs (e.g., microRNA21), SNPs in microRNAs binding site (e.g., rs4596 located within a target region of the predicted miR-518a-5p and miR-527), protein markers (e.g., carcinoembryonic antigen, N-methyltransferase), or microsatellites instability in tumors with deficient mismatch repair of some genes are among the most interesting and promising biomarkers.
Increasing evidence supports the use of combined fecal and serum biomarkers with sigmoidoscopy and colonoscopy screening in order to maximize the benefits and reduce the number of false-positive tests and patients undergoing invasive methods, which in turn could overcome the limitations of the current screening methods for early detection of CRC and adenomas.
结直肠癌（CRC）是全球主要的健康问题之一，且常被诊断为晚期。越来越多的证据表明，采用新型筛查方式对该疾病进行早期检测，可降低现有方法的依从性并提高其特异性。本综述的目的是概述目前可用的筛查方法（如粪便潜血试验（FOBT）、乙状结肠镜检查和结肠镜检查）及其优缺点，以及作为新型筛查方式的新的基因/表观遗传/蛋白质标志物。
有几种血清和粪便生物标志物可预测结直肠癌和息肉。粪便DNA标志物检测的总体灵敏度范围为53%至87%，而一组血清蛋白质标志物对结直肠癌的灵敏度/特异性高达85%。特别是，DNA甲基化标志物（如SEPT9、SFRP2和ALX4）、循环微小RNA（如微小RNA21）、微小RNA结合位点的单核苷酸多态性（如位于预测的miR-518a-5p和miR-527靶区域内的rs4596）、蛋白质标志物（如癌胚抗原、N-甲基转移酶），或某些基因错配修复缺陷的肿瘤中的微卫星不稳定性，都是最有趣且最有前景的生物标志物。
越来越多的证据支持将粪便和血清生物标志物与乙状结肠镜检查和结肠镜检查筛查相结合，以最大化益处并减少假阳性检测数量以及接受侵入性检查的患者数量，进而克服当前用于结直肠癌和腺瘤早期检测的筛查方法的局限性。
