Pre-operative Neo-adjuvant Chemotherapy Related miRNAs as Key Regulators and Therapeutic Targets in Colorectal Cancer

Abstract

Background: In colorectal cancer, the investigation of cancer pathogenesis and the determination of the relevant gene and gene pathways is particularly important to provide a basis for treatment-oriented studies. miRNAs which affect gene regulation in the molecular pathogenesis of cancer, have an active role in carcinogenesis. In the literature, miRNA expression levels have been associated with metastasis and prognosis in different cancers.

Objective: In our study, expression profiling of miRNAs involved in oncogenic and apoptotic pathways in patients with locally advanced colorectal cancer receiving neoadjuvant therapy was performed.

Methods: miRNAs were isolated from three different FFPE tissue samples taken at different times of the same patient (tumor tissue taken at the time of diagnosis, normal tissue samples, and after neoadjuvant therapy). The expression analysis of 84 miRNAs determined by PCR array (Fluidigm, USA) and mediated meta-analysis was performed comparatively to each study and non-cancerous control group. Evaluations were performed with ΔΔCT calculations.

Results: As a result of the miRNA PCR array study, in addition to differences were observed in miRNA expression between control and study groups. The potential biomarkers which were hsamiR- 215-5p, hsa-miR-9-59, hsa-miR-193a-5p, hsa-miR-206, hsa-miR-1, hsa-miR-96-5p have been detected for possible treatment resistance, prognosis and predispositions to cancers.

Conclusion: In patients with colorectal cancer, miRNA expression in the tumoral regions before and after neoadjuvant therapy has represented a variable pattern. It has been shown that miRNA studies can be used to predict the clinical course and response to treatment with differences in expression levels. It has been concluded that specific miRNAs may be candidate biomarkers for colorectal cancer.</p>.

Keywords: biomarker; colorectal cancer; expression profiling; microRNA; neoadjuvant therapy; therapeutic targets..