Wnt Signaling Pathway Related Gene CTNNBIP1 Act as A potential Prognostic Biomarker and A Comprehensive Prognostic Analysis in Osteosarcoma

Abstract

Abstract Purpose Osteosarcoma is the most common primary bone malignancy in children and young adults with poor outcomes in patients with recurrence and metastasis. The role of Wnt signaling pathway in osteosarcoma was complex and not well specified. Methods KEGG Wnt signaling pathway related genes were screened by univariate Cox regression analysis, Boruta feature selection and KM analysis in TARGET-OS cohort for the gene with the highest prognostic value in osteosarcoma. Clinical and immune cell infiltration features were also screened by univariate Cox regression, respectively. A prognostic model was established by the indicators screened above and evaluated in training and validation sets. Then, functional analysis of the differentially expressed genes were performed. Results CTNNBIP1 was screened as the KEGG Wnt signaling pathway related gene with the highest prognostic value in osteosarcoma. Metastasis, tumor site and M2 macrophage infiltration in tumor tissue were also identified as prognostic indicators. The model established by these indicators was evaluated in training set and successfully validated in validation set. C-index (0.812 in training set and 0.787 in validation set) and Calibration analysis suggested that the model had high prediction accuracy both in training and validation set. AUCs of the ROC analysis for 1-,3-,5-year prediction of the model were 0.96, 0.81 and 0.81 in training set, 0.80, 0.83 and 0.89 in validation set. Decision curve analyses also showed that patients could get high net benefit from the model. Functional analyses of the differential expressed genes between normal and osteosarcoma patients indicated that Wnt signaling pathway and cell cycle were upregulated and focal adhesion was downregulated in osteosarcoma patients. The overexpression of CTNNBIP1 in osteosarcoma tissues was validated by immunohistochemistry. Conclusions CTNNBIP1 was a potential prognostic gene and therapeutic target in osteosarcoma. Prognostic model established by CTNNBIP1, clinical and immune cell infiltration indicators had good prediction accuracy and discriminatory capacity.