Background: Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modi cation of tumor-associated proteins. However, its implication in the pathogenesis of osteosarcoma remains unclear. This study aimed to investigate the levels of O-GlcNAc and the expressions of O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA) in human osteosarcoma tissues and to nd correlations between the levels or expressions and several clinicopathologic parameters.Methods: Immunohistochemistry was conducted in 109 formalin-xed, para n-embedded bone tissue sections that were derived from 109 rst diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). Correlations between the imunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated.Results: A positive correlation was found between the IRS of OGA and the percentage of postchemotherapeutic tumor necrosis (r=0.308; P=0.017). Univariate analysis revealed signi cantly lower OGA IRS in metastatic patients (P=0.020) and poor chemotherapeutic-responder patients (P=0.001). By multivariate analysis, presence of tumor metastasis (P=0.002) and lower OGA IRS (P=0.004) was signi cantly associated with shorter overall survival. Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male gender (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were signi cantly correlated with short metastasis-free survival. But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006).Conclusions: O-GlcNAc pathway, especially OGA, involved in pathogenesis and aggressiveness of osteosarcoma. Low level of OGA expression may be used as a poor prognostic indicator.
BackgroundO-GlcNAcylation (O-GlcNAc) is a post-translational modi cation of proteins associated with regulation of various protein functions by an addition of N-acetylglucosamine (GlcNAc) to the hydroxyl group of serine or threonine residues of the target proteins. This modi cation is a dynamic and reversible process, strictly regulated by two important enzymes, O-linked N-acetylglucosamine transferase (OGT) and O-GlcNAcase (OGA), which add and remove the GlcNAc moieties, respectively. 1-5 O-GlcNAc is involved in many cellular processes, such as signal transduction, transcription, cell cycle control, and epigenetic control of gene expressions in response to stress and nutrient imbalance. 6,7 In this regard, O-GlcNAc homeostasis needs to be maintained in order to achieve proper cellular functions.Aberrations of O-GlcNAc are associated with the pathogenesis of many human diseases, including diabetes, neurodegenerative diseases and cancers. 6,[8][9][10][11] With respect to cancer pathogenesis and progression, several key players, such as p53, c-Myc, Forkhead box M1 (FoxM1) etc., have been shown to