Abstract:

Background and purpose: Colorectal cancer (CRC) is the most frequently occurring primary malignant tumor. Chemotherapy can reduce the risk of local and distant relapse. Therefore, it is very important to find new biomarkers that can predict chemoresistant and help in treatment decisions. Methods: In this study, we examined the expression levels of 1 200 human miRNAs in 6 CRC tissues, using miRNA profiling assay arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-4299, miR-196b, miR-324-5p, miR-455-3p and miR-939, by analyzing 100 specimens of stage Ⅳ colorectal adenocarcinoma (not respond and respond to the chemotherapy) to quantitative real-time PCR. We modeled the relationship between the expression levels of these miRNAs and the survival rate of 100 CRC patients by Kaplan-Meier method. Results: Expression profiles in CRCs suggested that 5 miRNAs were candidate markers associated with the chemoresistance of colorectal cancer. We found that miR-4299 and -196b had significant diagnostic value for chemoresistance CRC. miR-4299 yielded an AUC (the areas under the ROC curve) of 0.784 and miR-196b yielded an AUC of 0.647 in discriminating CRC from controls. Combined ROC analysis using these 2 miRNAs revealed an elevated AUC of 0.848 with 67.9% sensitivity and 90.9% specificity in discriminating chemoresistance CRC. The low level of miR-4299 expression and the high level of -196b expression are significantly correlated with the good survival of CRC patients. Conclusion: These data suggest that miR-4299 and -196b have strong potential as novel biomarkers for chemoresistant detection of colorectal cancer.

Key words: Colorectal cancer, Chemotherapy, Biomarkers, miR-4299, miR-196b