A Hypoxia Gene-Based Signature to Predict the Survival and Affect the Tumor Immune Microenvironment of Osteosarcoma in Children

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Abstract
Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

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