Osteosarcoma (OS) is the most common primary bone malignancy, predominately affecting children and adolescents. Due to the introduction of chemotherapy, the 5-year survival rate of OS patients has dramatically improved to 60-70%. Unfortunately, OS patients with recurrence or metastatic disease have less than a 20% chance of long-term survival, despite aggressive therapies. In this study, we aimed to identify gene expression patterns associated with metastasis and recurrence in order to identify potential biomarkers with prognostic power. We found that high expression of polyglutamine tract-binding protein 1 (PQBP1) and low expression of phosphoenolpyruvate carboxykinase 2 (PCK2) were related to a high probability of recurrence and metastasis in OS patients and also predicted shorter recurrence-free survival (RFS) and metastasis-free survival (MFS) after adjustment for other clinical variables. Prediction models based on the combination of PQBP1 and PCK2 expression had good and robust predictive power for recurrence and metastasis. A PQBP1 and PCK2-centered protein interaction network was built, and the hypothetical regulatory path between them was identified and termed the PQBP1-SF3A2-UBA52-PCK2 axis. Gene enrichment analysis indicated that aberrations of metabolism might play an important role in recurrence and metastasis in OS patients. Accordingly, PQBP1 and PCK2 are crucial for recurrence and metastasis in OS, and these findings provide a molecular basis for the exploitation of diagnostic and therapeutic strategies for overcoming recurrence and metastasis in OS.
Keywords: PCK2; PQBP1; metastasis; osteosarcoma; recurrence.