Abstract:
Objective This work aimed to investigate the role of the runt-related transcription factor 2(RUNX2) gene in the pathogenesis, progression, and prognosis of osteosarcoma by detecting the variance of RUNX2 copy number and its protein expression.
Methods Array-based comparative genomic hybridization was used to detect changes in DNA copy number in 10 cases of fresh osteosarcoma tissues, focusing on the RUNX2 gene status.The RUNX2 protein expression levels of 59 osteosarcoma cases were assayed by IHC, using formalin-fixed and paraffin-embedded osteosarcoma tissues.
Results RUNX2 gene amplification was observed in 3 of the 10 specimens of osteosarcoma(30%).The positive rate of RUNX2 protein expression was 50.8% of 59 cases with osteosarcoma(30/ 59).RUNX2 protein expression level was not significantly associated with clinicopathological features and survival rate(P > 0.05) in the osteosarcoma patients.The Kaplan-Meire univariate survival analysis showed that the pathologic TNM stage(pTNM); the diagnosis, recurrence, and metastasis of the cancer; and multidisciplinary therapy had significant effects on the patients' disease-free survival.This analysis also showed that sex, pTNM stage, neoadjuvant chemotherapy, and cancer metastasis had significant effects on the patients' overall survival(P < 0.05).However, the COX model multivariate survival analysis showed that these factors could not be used as the independent predictor for survival.
Conclusion RUNX2 gene amplification, elevated protein expression, and lack of association between the clinical characteristics and prognosis of osteosarcoma patients indicate that RUNX2 gene amplification and over-expression of proteins may comprise the initial stages of the pathogenesis of osteosarcoma.