Hypoxia-immune-related microenvironment prognostic signature for osteosarcoma

缺氧免疫相关微环境对骨肉瘤的预后特征

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作者:Wenshuo Zhang, Pang Lyu, Darja Andreev, Yewei Jia, Fulin Zhang, Aline Bozec

Conclusion

The hypoxia-immune-based prognostic signature might contribute to the optimization of risk stratification for survival and personalized management of osteosarcoma patients.

Methods

The individual hypoxia and immune status of osteosarcoma patients were identified with transcriptomic profiles of a training cohort from the TARGET database using ssGSEA and ESTIMATE algorithms, respectively. Lasso regression and stepwise Cox regression were performed to develop a hypoxia-immune-based gene signature. An independent cohort from the GEO database was used for external validation. Finally, a nomogram was constructed based on the gene signature and clinical features to improve the risk stratification and to quantify the risk assessment for individual patients.

Results

Hypoxia and the immune status were significantly associated with the prognosis of osteosarcoma patients. Seven hypoxia- and immune-related genes (BNIP3, SLC38A5, SLC5A3, CKMT2, S100A3, CXCL11 and PGM1) were identified to be involved in our prognostic signature. In the training cohort, the prognostic signature discriminated high-risk patients with osteosarcoma. The hypoxia-immune-based gene signature proved to be a stable and predictive method as determined in different datasets and subgroups of patients. Furthermore, a nomogram based on the prognostic signature was generated to optimize the risk stratification and to quantify the risk assessment. Similar results were validated in an independent GEO cohort, confirming the stability and reliability of the prognostic signature.

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