Evaluation of the impact of microrna variants on prognosis and treatment responses in patients wi̇th multiple myeloma undergoing autologous stem cell transplantation

Background and aim: Multiple myeloma (MM) is a malignant plasma cell neoplasm. MicroRNA(miRNA, miR-, mi-)s are short, single-stranded, approximately 21-23 nucleotides in length and noncoding RNA molecules. Their main function is regulation of gene expression in the translation stage. There are studies in the literature, about the effects of impaired regulation of miRNA expression and miRNA related polymorphisms on the prognosis and pathogenesis in MM. MiRNA196a2 gene is localized in chromosome 12q13.13 and miRNA196a2 has been the subject of many recent studies related to malignancy. In this study we aimed to evaluate the impact of miRNA196a2 polymorphisms on prognosis and treatment responses in patients with MM undergoing autologous haematopoietic stem cell trasplantation (AHSCT). Materials and Methods: A total of 200 patients with MM and 200 healthy controls were included in the study. Patient group consisted of patients, followed by Gaziantep University Medical Faculty, Sahinbey Research and Practice Hospital Hematology Clinic, between 15.06.18-15.10.2018. Clinical data were evaluated with retrospective file screening. DNA of patients (with/without AHSCT) and healty controls, was isolated from the venous blood sample. DNA samples were stored at -20 0C. MiRNA196a2 genotyping was performed with the polymerase chain reaction (PCR) – restriction fragment length polymorphism (RFLP) technique. No intervention was made to the patients included to the study in follow-up and treatment. Survivals to the progression and long-term survival were followed. MiRNA196a2 allels/genotypes distributions were compared in patients and healty controls. The effects of genotype and prognostic factors on overall survival (OS) and progression free survival (PFS) were evaluated. Findings: There was no significant difference between the genotype distributions of MM patients and healty controls. No relation was found between genotype distribution and clinical parameters (age, gender, ECOG performance status, ISS stage, Ig subgroups). In univariate analysis; gender, ECOG performance status, underwenting AHSCT were found to have a significant effect on PFS. Gender, age, ISS stage, light chain type, ECOG performance status, underwenting AHSCT, miRNA196a2 genotype were found to have a significant effect on OS. In multivariate analysis, only factor effecting PFS was underwenting AHSCT (p=0.001) and ECOG performance status (p=0.016), miRNA196a2 genotype (p=0.041), ISS stage (0.045) were found to have a significant effect on OS. Results: It's shown that mi196a2 polymorphisms effects OS in MM and this effect is statistically significant. CC genotype was found to be worse prognostic finding. It was concluded that patients with CC genotype can be evaluated in terms of more aggressive treatment options in the early period. Keywords: Multiple myeloma, autologous haematopoietic stem cell trasplantation, miRSNPs, microRNA, miR196a2 polymorphism