Identification of serum microRNA profiles in colon cancer

Abstract

Background: microRNAs (miRNAs) exist in blood in an apparently stable form. We have explored whether serum miRNAs can be used as non-invasive early biomarkers of colon cancer.

Methods: Serum samples from 30 patients with colon cancer stage IV and 10 healthy controls were examined for the expression of 375 cancer-relevant miRNAs. Based on the miRNA profile in this study, 34 selected miRNAs were measured in serum from 40 patients with stage I-II colon cancer and from 10 additional controls.

Results: Twenty miRNAs were differentially expressed in serum from stage IV patients compared with controls (P<0.01). Unsupervised clustering revealed four subgroups; one corresponding mostly to the control group and the three others to the patient groups. Of the 34 miRNAs measured in the follow-up study of stage I-II patients, 21 showed concordant expression between stage IV and stage I-II patient. Based on the profiles of these 21 miRNAs, a supervised linear regression analysis (Partial Least Squares Regression) was performed. Using this model we correctly assigned stage I-II colon cancer patients based on miRNA profiles of stage IV patients.

Conclusion: Serum miRNA expression profiling may be utilised in early detection of colon cancer.

Figure 1

Heat-map diagram of a two-way hierarchical clustering analysis consisting of the 20 most differentially expressed miRNAs in serum from 30 metastatic (stage IV) colon cancer patients as compared with 10 healthy subjects (P-value <0.01). Red colour represents an expression level above mean, blue colour represents expression lower than the mean. Upper colour labelling show patient samples in red and controls in green.

Figure 2

Differentially expressed miRNAs in stage IV (red bars) vs stage I–II (blue bars) colon cancer. The expression of 34 miRNAs was compared, and 26 miRNAs were detected. In all, 21 of 26 detected miRNAs showed the same expression profile in early-stage I–II vs metastatic stage IV colon cancer.

Figure 3

Prediction analysis of early-stage colon cancer patients. Controls are shown in red and cancer samples in blue. 9 out of 10 healthy controls were correctly predicted as true negatives and 35 out of 40 patients with cancer as true positives.