Two novel predictive biomarkers for osteosarcoma and glycolysis pathways: A profiling study on HS2ST1 and SDC3.

Introduction: Prognostic biomarkers for osteosarcoma (OS) are still very few, and this study aims to examine 2 novel prognostic biomarkers for OS through combined bioinformatics and experimental approach.

Materials And Methods: Expression profile data of OS and paraneoplastic tissues were downloaded from several online databases, and prognostic genes were screened by differential expression analysis, Univariate Cox analysis, least absolute shrinkage and selection operator regression analysis, and multivariate Cox regression analysis to construct prognostic models. The accuracy of the model was validated using principal component analysis, constructing calibration plots, and column line plots. We also analyzed the relationship between genes and drug sensitivity. Gene expression profiles were analyzed by immunocytotyping. Also, protein expressions of the constructed biomarkers in OS and paraneoplastic tissues were verified by immunohistochemistry.

Results: Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) and Syndecan 3 (SDC3, met all our requirements after screening. The constructed prognostic model indicated that patients in the high-risk group had a much lower patient survival rate than in the low-risk group. Moreover, these genes were closely related to immune cells (P < .05). Drug sensitivity analysis showed that the 2 genes modeled were strongly correlated with multiple drugs. Immunohistochemical analysis showed significantly higher protein expression of both genes in OS than in paraneoplastic tissues.

Conclusions: HS2ST1 and SDC3 are significantly dysregulated in OS, and the prognostic models constructed based on these 2 genes have much lower survival rates in the high-risk group than in the low-risk group. HS2ST1 and SDC3 can be used as glycolytic and immune-related prognostic biomarkers in OS.