Abstract
BackgroundScreening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups.MethodsThe expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues.ResultsHigh levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed.ConclusionWe identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1327-5) contains supplementary material, which is available to authorized users.
Highlights
Screening for the early detection of colorectal cancer is important to improve patient survival
Forty miRNAs were significantly different in advanced cancer, 22 in early stage cancer, 7 in adenoma, and 22 in the polyp group compared to normal controls
Ten miRNAs were significantly altered in both the early stage and advanced cancer groups compared to the normal controls; miR-923, miR-801, miR-144*, miR-135a*, miR-500, miR497, miR-150, miR-30c and RNU48 showed lower levels while miR-532-3p was more abundant in the cancer groups compared to the controls
Summary
Screening for the early detection of colorectal cancer is important to improve patient survival. CRC develops in a progressive fashion during which normal colon epithelial cells transform to form benign growths such as polyps. These polyps may progress to benign adenomas, and to invasive cancer lesions. Screening at risk populations for CRC has significantly improved the outcome for patients, for instance diagnosis while the disease remains localised to the colon dramatically improves patient survival, and removal of early lesions such as adenomatous polyps may prevent disease formation [4]. FOBT is a simple, cheap and safe test that relies on the assumption that large adenomas and cancerous lesions may bleed, and that these blood products are detectable in the faecal matter of patients. The other examinations involve more costly and invasive procedures which allow direct access to colorectal lesions
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