Investigation of the relationship of genetic and chromosome changes with metastasis in osteosarcoma patients

Osteosarcoma (OS) is a primary bone tumor originating from primitive osteogenic mesenchymal cells. OS usually has poor prognosis and high mortality. The presence of metastasis, high recurrence rate and limitation of movement are among the important clinical findings of OS. Although chemotherapy is essential, its effectiveness is low. Metastatic OS (MOS) patients' prognosis is severe along with the response to treatment. Therefore, clarifying molecular mechanisms and determining different treatment approaches are important for improving the clinical course. For this purpose, cyclin-dependent kinase inhibitor-3 (CDKN3), protein regulator of cytokinesis-1 (PRC1), ribonucleotide-reductase catalytic subunit-M1 (RRM1), epidermal growth factor containing fibulin-like extracellular matrix protein-2 (EFEMP2), eukaryotic translation initiation factor-4-gamma-2 (EIF4G2) and melanoma associated-antigen-3(MAGEA3) genes in OS and MOS cases were evaluated. Relative mRNA expression levels were showed that PRC1 and EFEMP2 expressions elevated and statistically significant (p<0.0001 and p=0.0008,respectively). For better understanding of PRC1's role, protein levels by immunohistochemistry and chromosome 15 numerical anomalies by fluorescent in situ hybridization were examined. High PRC1 protein expression was associated with shortened survival time in MOS. It was also found that copy number of chromosome 15 significantly increased in MOS. In vitro RNA interference assays showed that silencing PRC1 in the Saos-2 cell line led cell cycle arrest at the G2/M phase and induced apoptosis. In conclusion, due to its clinicopathological and metastasis relation, the role of PRC1 in the pathogenesis of OS has been shown and it has been found that it has a high potential in the treatment of malignancy as a prognostic marker.