YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma

We studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate analysis was performed using Cox proportional hazard regression to evaluate the correlation between YY1 expression and both metastasis development and mortality.YY1 protein is not usually present in normal bone; in contrast, a high number of patients (61%) showed a high score of YY1 positive cells (51-100%) and 39% had a low score (10-50% positive cells). No statistical difference was found in histology, anatomic sites, or response to chemotherapy between the two degrees of YY1 expression. Cox regression analysis demonstrated that the highest score of YY1 expression was predictive of both low metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI = 1.863-37.451 p = 0.006) regardless of the effects of covariates such as age, gender, histology and chemonecrosis.Overexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome.Osteosarcoma is the most common primary malignant bone tumor in adolescents and children [1]. It occurs frequently in long bones and metastasizes preferentially to the lung [1]. Despite recent advances in chemotherapy, the 5-year event-free survival and overall survival rates, closely linked to grade of osteosarcoma, are around 50-60%. This is due to the development of resistance to multiple types of chemotherapy and radiotherapy [2-4]. Clinical stage of the disease and several clinical biomarkers have been correlated with the outcome [5-11]. Nonetheless, these prognostic factors have limited utility in terms of predicting survival [12].The ubiquitous, conserved, multifunctional polycomb transcription factor Yin Yang 1 (YY1) plays a pivotal role in biological processes [13-15]. YY1 regulates embryonic blood formation and its downstream hox genes, X chromosome inactivation, differentiation, and cell cycle [13,14]. The majority of the data are consi