Relationship Between O-GlcNAcase Expression and Prognosis of Patients With Osteosarcoma.

Abstract

Several studies have demonstrated a role of O-GlcNAcylation (O-GlcNAc) in tumorigenesis of various carcinomas by modification 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, by using immunohistochemistry; and to find correlations between the levels or expressions and several clinicopathologic parameters. There were 109 first diagnosed osteosarcoma patients, including Enneking stage IIB (n=70) and III (n=39). Correlations between the immunoreactive score (IRS) and clinicopathologic parameters, overall survival, and metastasis-free survival were evaluated. 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 significantly 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 significantly associated with shorter overall survival. Subgroup analysis in stage IIB osteosarcoma (n=70) demonstrated that male sex (P=0.019), presence of tumor recurrence (P=0.026), poor chemotherapeutic responder (P=0.022), and lower OGA IRS (P=0.019) were significantly correlated with short metastasis-free survival. But, lower OGA IRS was the only independent predictor for short metastasis-free survival (P=0.006). Our findings suggested that O-GlcNAc pathway, especially OGA, may involve in pathogenesis and aggressiveness of osteosarcoma. Low level of OGA expression may be used as a poor prognostic indicator.

• Authors: Thamonwan Sombutthaweesri, Shuangjiang Wu, Nutchapon Chamusri, Jongkolnee Settakorn, Dumnoensun Pruksakorn, Parunya Chaiyawat, Thanapat Sastraruji, Suttichai Krisanaprakornkit, Chayarop Supanchart
• Journal: Applied immunohistochemistry & molecular morphology : AIMM (Appl Immunohistochem Mol Morphol) Vol. 30 Issue 1 Pg. e1-e10 (01 01 2022) ISSN: 1533-4058 [Electronic] United States
• PMID: 34469899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• hexosaminidase C
• beta-N-Acetylhexosaminidases

Topics

• Humans
• Male
• Neoplasm Recurrence, Local
• Osteosarcoma
• Protein Processing, Post-Translational
• beta-N-Acetylhexosaminidases (genetics, metabolism)