Abstract
Osteosarcoma represents one of the most aggressive tumors of bone among adolescents and young adults. Despite improvements in treatment, osteosarcoma has a grave prognosis. The identification of prognostic factors is still in its infancy. Weighted gene correlation network analysis (WGCNA) was conducted on mRNA-sequencing and clinical information (gender, survival and metastasis) of osteosarcoma patients from the TARGET database to obtain genes in modules associated with metastasis of osteosarcoma. The Cox regression analysis was then performed on the gene expression profile from TARGET to screen genes associated with patients’ survival. Known genes related to osteosarcoma were obtained by intersecting osteosarcoma-related genes from DisGeNET and DiGSeE, followed by the construction of PPI network of osteosarcoma-related genes and survival-related genes in modules. The screened key genes were subject to multi-factor Cox proportional hazards model, and osteosarcoma patients were classified into high- and low- risk groups according to the risk score to evaluate the potential of key genes to predict the survival of osteosarcoma patients. The WGCNA showed that 4 genes in tan and 19 genes in pink modules were related to the survival of osteosarcoma patients. Osteosarcoma-related known genes (9) were obtained in intersection of DisGeNET and DiGSeE. PPI network identified 4 key genes (KRT5, HIPK2, MAP3K5 and CD5) closely associated with survival of osteosarcoma patients. HIPK2, MAP3K5 and CD5 expression was inversely correlated with survival risk, while KRT5 expression was positively correlated with survival risk. These results show KRT5, HIPK2, MAP3K5 and CD5 serve as prognostic factors of osteosarcoma patients.
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Yuan Li and Fengxiao Ge participated in the conception and design of the study. Yuan Li, Fengxiao Ge and Shuaihua Wang performed the analysis and interpretation of data. Yuan Li, Fengxiao Ge and Shuaihua Wang contributed to drafting the article. Yuan Li and Fengxiao Ge revised it critically for important intellectual content. Shuaihua Wang is the GUARANTOR for the article who accepts full responsibility for the work and/or the conduct of the study, had access to the data, and oversaw the decision to publish.
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Li, Y., Ge, F. & Wang, S. Four genes predict the survival of osteosarcoma patients based on TARGET database. J Bioenerg Biomembr 52, 291–299 (2020). https://doi.org/10.1007/s10863-020-09836-6
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DOI: https://doi.org/10.1007/s10863-020-09836-6