MicroRNA (
miRNA) profiling represents a promising source of
cancer-related
biomarkers.
miRNA signatures are specific for each
cancer type and subgroups of patients with diverse treatment sensitivity. Yet this
miRNA potential has not been satisfactorily explored in
rectal cancer (RC). The aim of the study was to identify the specific
miRNA signature with clinical and therapeutic relevance for RC. Expressions of 2555
miRNA were examined in 20 pairs of
rectal tumors and matched non-malignant tissues by 3D-Gene Toray microarray. Candidate
miRNAs were validated in an independent cohort of 100 paired rectal tissues and in whole plasma and exosomes of 100 RC patients. To study the association of
miRNA profile with therapeutic outcomes, plasma samples were taken repeatedly over a time period of 1 year reflecting thus patients' treatment responses. Finally, the most prominent
miRNAs were investigated in vitro for their involvement in cell growth. We identified RC-specific
miRNA signature that distinguishes responders from non-responders to
adjuvant chemotherapy. A predominant part of identified
miRNAs was represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, -18b, -19a, -19b, -20a, -20b and -106a in
tumor was associated with higher risk of
tumor relapse and their overexpression in RC cell lines stimulated cellular proliferation. Examination of these
miRNAs in plasma exosomes showed that their levels differed between RC patients and healthy controls and correlated with patient's treatment response.
miRNAs from miR-17/92 cluster represent a non-invasive
biomarker to predict posttreatment prognosis in RC patients.