Circulating microRNAs as biomarkers of colorectal cancer: results from a genome-wide profiling and validation study

Abstract

Background & aims: Circulating microRNAs (miRNAs/miRs) might be used as biomarkers for the diagnosis of cancer and other diseases. Noninvasive approaches are needed to complement and improve upon current strategies for colorectal cancer (CRC) screening. We investigated whether plasma levels of miRNA can differentiate patients with CRC from healthy individuals. We also investigated whether plasma samples from patients with premalignant neoplastic lesions, such as advanced adenomas (AAs), also had a different expression pattern of miRNAs.

Methods: We analyzed 196 plasma samples from 123 patients newly diagnosed with sporadic colorectal neoplasia (63 with CRC and 60 with AAs) and 73 healthy individuals (controls) seen at 2 tertiary medical centers in Spain. An initial set of samples was analyzed using a genome-wide miRNA expression profiling assay (n = 61). Quantitative reverse-transcription PCR was used to validate the expression of selected miRNAs in an independent cohort (n = 135).

Results: Patients with CRC or AAs had plasma miRNA expression profiles that differed significantly from those of controls. We selected a group of 13 miRNAs for validation in an independent cohort of patients; 6 (miR18a, miR19a, miR19b, miR15b, miR29a, and miR335) were confirmed to be significantly up-regulated in patients with CRC, differentiating patients with CRC from controls with area under the receiver operating characteristic curve values ranging from 0.80 (95% confidence interval [CI], 0.71-0.89) to 0.70 (95% CI, 0.59-0.80). Only miR18a was confirmed to be significantly up-regulated in patients with AAs, compared with controls; the area under the receiver operating characteristic curve value was 0.64 (95% CI, 0.52-0.75).

Conclusions: Patients with CRC have significantly different patterns of miRNA expression than healthy individuals. These patterns might be developed as biomarkers for CRC, although they have limited value in identifying patients with premalignant neoplastic lesions.