Specific microRNAs as novel biomarkers for combination chemotherapy resistance detection of colon adenocarcinoma

Jinsong Hu, Ye Xu, Sanjun Cai

Colon cancer is a 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 chemoresistance and help in individuate treatment decision. Retrospective analysis of 126 patients, who were treated at our department between June 2010 and December 2014. In this study, we examined the expression levels of 1200 human miRNAs in colon cancer tissues, using laser capture microdissection and microRNA profiling 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, through analyzing stage IV colon adenocarcinoma tissues (not responding and responding to the chemotherapy) with laser capture microdissection and quantitative real-time PCR. We analyze the relationship between the expression levels of these miRNAs and the survival rate of colon cancer patients by Kaplan-Meier method. We found that miR-4299 and -196b have significant diagnostic value in chemoresistant colon cancer. MiR-4299 yielded an AUC (the areas under the ROC curve) of 0.810 and miR-196b yielded an AUC of 0.726 in discriminating chemoresistant colon cancer from controls. Combined with ROC analyses of these 2 miRNAs revealed an elevated AUC of 0.877 with 71.4 % sensitivity and 95.5 % specificity in discriminating chemoresistant colon cancer. The low level of miR-4299 expression and the high level of -196b expression are significantly correlated with better survival of colon cancer patients. These data suggest that miR-4299 and -196b have strong potential as novel biomarkers for chemoresistance detection of colon cancer.