Circulating MicroRNAs in Cancer

Abstract

Background. The identification of response in locally advanced rectal cancer (RC) to a 5-FU based chemoradiotherapy is a crucial step towards an individualization of the therapy. The impact of microRNAs (miRNAs) on progression or resistance in cancer has recently been described. Although their impact in patients' blood has recently been described in different cancer types data in rectal cancer are scarce. Materials and methods. miRNAs were extracted from patient and healthy control plasma including C. elegans miRNA mimics for the normalisation process. Each miRNA was detected using SYBR-Green based miScript PCR system from Qiagen. 15 differentially regulated miRNAs that were retrieved from the comparison of rectal cancer and normal tissue based on miRNA microarray analyses were analysed in a first set of 17 patients. All patients were treated within the CAO/ARO/AIO-94 and -04 trial of the German Rectal Cancer Study Group. Additionally, 14 age and gender matched healthy controls were analysed. In a second set of 46 controls and 122 patients a subset of miRNAs was validated and analysed on postsurgical blood specimens. Results. 5 of the 15 analyzed miRNAs turned out to be significantly down regulated in plasma compared to healthy controls (miR-17, miR- 18b, miR-20a, miR-31 and miR-193a-3p). Subsequently, a second set of patients was analysed and two of the previously identified miRNAs could be validated in this independent cohort. Interestingly, all miRNAs were downregulated in the RC patients. Comparing pretherapeutical and postsurgical expression 4 out of 5 miRNAs were significantly differentially expressed. Conclusion. This study demonstrates for the first time the differential expression of plasma miRNAs in RC patients compared to healthy controls. To assess the impact of miRNAs on response or prognosis prediction these results will be correlated to the clinical data and a more comprehensive approach will be undertaken.