MiR-155 and miR-34a expression levels in mycosis fungoides.
Project no. 20226 · Status: Kapanmış (Yayın bekleniyor) · 2018
Summary
Aim: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphomas. The classic type of MF is clinically seen in three different stages as patch, plaque and tumor. Histopathological findings may not be decisive in the patch stage and can be confused with inflammatory dermatoses. Recurrent biopsies may be required for early diagnosis and the average time is 4-6 years until a definitive diagnosis is made. Although the etiopathogenesis of MF is not clearly known, it is accepted that genetic, environmental, infectious and immunological factors play a role. Genetic studies have shown genetic and epigenetic changes in tumor suppressor and apoptosis regulating genes. There are few studies in the literature about the role of miRNAs, one of the epigenetic regulators in cutaneous lymphomas. Although there are some studies supporting the oncogenic role of MiR-155 and miR-34a in MF, no strong data have been published yet. The aim of this study is; to analyze miR-155 and miR-34a expression levels in skin biopsy materials of MF patients and control group, to compare MF patients with control group, as well as to compare miRNA expression levels at different stages of MF, to contribute to the elucidation of the pathogenesis of the disease, to obtain the necessary data to use microRNAs as a potential biomarkers. Material and Methods: The study included patients aged between 19-95 years who were admitted to Ege University Faculty of Medicine Hospital Dermatology and Venerology Outpatient Clinic between January 2004 and December 2018. The study group consisted of 40 patients who were clinically and histopathologically diagnosed with MF and as a control group, 40 patients who had a large re-excision due to non-MF skin tumor, without tumor in the re-excision material. Archived biopsy materials of the patient and control groups were used in the study. The gender and age of the patient and control groups and the duration of disease, clinical type, histopathological findings and mortality were evaluated. After removing paraffin from samples, total RNA isolation, complementary DNA (cDNA) synthesis were performed and miR-155 and miR-34a expressions were evaluated by Real-Time Quantitative Revers Transcriptase Polymerase Chain Reaction (RT-QPCR). The statistical analysis of the obtained results was performed by ?/?Ct method. Results: There was an increase in miR-155 expression in the patient group compared to the control group. When grouped separately according to clinical lesions and histopathological findings, it was found that the greatest increase was in plaque lesions and histopathologically in patients with plaque stage MF. There was a decrease in the expression of miR-34a in clinical group with tumors, and histopathologically in patients with tumor stage MF. It was observed that miR-155 expression increased as the disease duration increased. As the disease duration increased, there was a significant increase in miR-155 fold changes in the group with plaque lesions and miR-34a fold changes in the group with patch lesions (p <0.00001, p <0.0001); there was a significant decrease in miR-34a fold changes in the group with tumoral lesions (p <0.001). Conclusion: It was thought that miR-155 and miR-34a may have effective roles in the transition from patch stage to plaque stage, and the difference between the results of previous studies may be related to genetic differences between populations and interactions between genes. An increase in microRNA expression with prolongation of disease duration was attributed to increased clonal T cell density in the lesions. Significant changes in microRNA expression in clinical groups according to the duration of disease may be guiding in the selection of patients in whom miR-targeted therapies will be administered. Further studies are needed to make a complete assessment of microRNA expression change according to disease duration.