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Comprehensive analysis of hypoxia-related genes for prognosis value, immune status, and therapy in osteosarcoma patients

骨肉瘤 列线图 医学 比例危险模型 肿瘤科 间质细胞 小桶 内科学 生物信息学 基因 基因表达 转录组 癌症研究 生物 遗传学
作者
Tao Han,Zhouwei Wu,Zhe Zhang,Jinghao Liang,Chuanpeng Xia,Hede Yan
出处
期刊:Frontiers in Pharmacology [Frontiers Media SA]
卷期号:13 被引量:5
标识
DOI:10.3389/fphar.2022.1088732
摘要

Osteosarcoma is a common malignant bone tumor in children and adolescents. The overall survival of osteosarcoma patients is remarkably poor. Herein, we sought to establish a reliable risk prognostic model to predict the prognosis of osteosarcoma patients. Patients ’ RNA expression and corresponding clinical data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus databases. A consensus clustering was conducted to uncover novel molecular subgroups based on 200 hypoxia-linked genes. A hypoxia-risk models were established by Cox regression analysis coupled with LASSO regression. Functional enrichment analysis, including Gene Ontology annotation and KEGG pathway analysis, were conducted to determine the associated mechanisms. Moreover, we explored relationships between the risk scores and age, gender, tumor microenvironment, and drug sensitivity by correlation analysis. We identified two molecular subgroups with significantly different survival rates and developed a risk model based on 12 genes. Survival analysis indicated that the high-risk osteosarcoma patients likely have a poor prognosis. The area under the curve (AUC) value showed the validity of our risk scoring model, and the nomogram indicates the model’s reliability. High-risk patients had lower Tfh cell infiltration and a lower stromal score. We determined the abnormal expression of three prognostic genes in osteosarcoma cells. Sunitinib can promote osteosarcoma cell apoptosis with down-regulation of KCNJ3 expression. In summary, the constructed hypoxia-related risk score model can assist clinicians during clinical practice for osteosarcoma prognosis management. Immune and drug sensitivity analysis can provide essential insights into subsequent mechanisms. KCNJ3 may be a valuable prognostic marker for osteosarcoma development.
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