http://www.ncbi.nlm.nih.gov/pubmed/23267864

Clin Gastroenterol Hepatol. 2012 Dec 22. pii: S1542-3565(12)01509-1. doi: 10.1016/j.cgh.2012.12.009. [Epub ahead of print]

Circulating MicroRNAs as Biomarkers of Colorectal Cancer: Results from a Genome-Wide Profiling and Validation Study.

Giráldez MD, Lozano JJ, Ramírez G, Hijona E, Bujanda L, Castells A, Gironella M.

Source

Department of Gastroenterology, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Spain.

Abstract

BACKGROUND & AIMS:

Circulating microRNAs (miRNAs or miRs) might be used as biomarkers for diagnosis of cancer and other diseases. Non-invasive 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) had also 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). Real-time quantitative reverse-transcriptase PCR was used to validate the expression of selected miRNAs in an independent cohort (n=135).

RESULTS:

Patients with CRC or AA 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 (AUCROC) 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 upregulated in patients with AA, compared with controls, with an AUCROC curve value of 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.