Identification and preliminary validation of a four-gene signature to predict metastasis and survival in osteosarcoma.

Osteosarcoma is a primary malignant bone tumor that occurs frequently in children and adolescents and has a propensity for drug resistance, recurrence, and metastasis. The purpose of this study was to identify potential target genes to predict metastasis and survival in patients with osteosarcoma. We analyzed gene expression profiles and corresponding clinical data of patients with osteosarcoma in the Gene Expression Omnibus database and identified 202 genes that were differentially expressed between osteosarcoma cells and normal osteoblasts. Univariate and multivariable Cox regression analyses identified four risk genes that affected osteosarcoma prognosis: MCAM, ENPEP, LRRC1, and CPE. Independent prognostic analyses and clinical correlation studies showed that the four risk genes constituted an independent prognostic signature that correlated with survival and clinical parameters including age and distant metastasis. In a single-sample Gene Set Enrichment Analysis, risk scores based on the prognostic signature correlated with tumor infiltration by immune cells and immune functions in osteosarcoma. A subsequent analysis showed that the expression levels of the four genes in the prognostic signature were predictive of overall survival and metastasis-free survival of patients with osteosarcoma. Furthermore, Human Cancer Metastasis Database and qRT-PCR analyses demonstrated that the four risk genes are overexpressed in osteosarcoma tissues and cell lines. In summary, we developed and validated a four-gene prognostic signature that may be useful in osteosarcoma diagnosis and metastasis prediction. AJTR