Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma

Abstract

AbstractOsteosarcoma is a common malignant bone tumor characterized by the production of osteoid stroma by the tumor. However, effect of IGFBP4 and TAGLN on the survival of osteosarcoma is unclear. The GEO database was used to identify the differentially expressed genes (DEGs) between control samples and osteosarcoma. Genes for biological process (BP), cellular composition (CC), and molecular function (MF) were examined using DAVID, Metascape, and GSEA. GSE14359 and GSE36001 were downloaded in the GEO database. GEO2R was used to find DEGs between control samples and osteosarcoma. The cytoHubb also found the hub genes of IGFBP4 and TAGLN. The Kaplan–Meier method was used to analyze overall survival. A total of 134 patients with osteosarcoma were enrolled in this study. The RNA levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN expression and their associations with clinical indicators were analyzed using Spearman's rho test and Pearson's Chi-squared test. Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors. And the animal model was used to verify the role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed to construct the correlation among the expression of IGFBP4, TAGLN, and osteosarcoma. Through bioinformatics, IGFBP4 and TAGLN were identified as the hub genes of osteosarcoma. And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels. The results showed that pathologic grade (P = 0.017), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly correlated with IGFBP4. Also, pathologic grade (P = 0.002), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly related to the TAGLN. Spearman’s correlation coefficient displayed that IGFBP4 were significantly correlated with the tumor metastasis (ρ = − 0.843, P < 0.001), enneking stage (ρ = − 0.500, P < 0.001), and TAGLN (ρ = 0.821, P < 0.001). IGFBP4 (HR = 0.252, 95% CI 0.122–0.517, P < 0.001) and TAGLN (HR = 0.155, 95% CI 0.089–0.269, P < 0.001) were significantly associated with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the osteosarcoma tissue than the control group. And the SVM presented that there exists strong relationship among the expression of IGFBP4, TAGLN, and osteosarcoma. IGFBP4 and TAGLN may be attractive molecular targets for osteosarcoma, opening a new avenue for research into the disease.