TYRO Protein Tyrosine Kinase-binding Protein Predicts Favorable Overall Survival in Osteosarcoma and Correlates With Antitumor Immunity

Abstract

Objective: To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Methods: Firstly, the expression of TYROBP was analyzed using the t-test. The Kaplan-Meier plotter analysis and a receiver operating characteristic (ROC) curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. Results: TYROBP was significantly increased in osteosarcoma (all P <0.001). However, the high expression of TYROBP was related to better OS of osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P =0.005), especially in patients with male sex, age <18 years, metastasis, and tumor site leg/foot (all P <0.05). Besides, TYROBP mRNA expression was significantly associated with tumor site (P <0.01) but had no remarkable relationship with age, gender, and metastasis status (all P>0.05). Functional annotation and GSEA revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P <0.001, r=0.87). Conclusions: TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.