Co-expression of CD44v6 and MMP2 predicts lung metastasis and unfavorable prognosis in osteosarcoma

Aim: To evaluate the prognostic significance of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) expression in patients with surgically resected osteosarcoma. Methods: CD44v6 and MMP2 expression were immunohistochemically detected in 113 primary osteosarcoma patients at our institute between 2001 and 2019. Results: Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival. An extended predictive range and improved sensitivity were observed when the combined effects of CD44v6 and MMP2 were considered. Specifically, patients with CD44v6+ and MMP2+ expression were more susceptible to lung metastasis and exhibited the poorest survival rates compared with the other groups. Conclusion: The combination of CD44v6 and MMP2 may serve as a precise prognostic indicator for predicting metastatic progression and survival outcomes in patients with osteosarcoma. Plain language summary: The most common type of bone cancer in children, teens and young adults is osteosarcoma, which often spreads to the lungs. With proper chemotherapy and surgery, many patients can recover, but if the diagnosis and treatment process go wrong, it could have serious consequences. The most common symptoms of osteosarcoma in its early stages are pain and swelling. The pain usually comes and goes, which can be easily mistaken for growing pains, resulting in a delayed diagnosis. In patients with metastatic (cancer cells spreading from the primary site to other parts of the body) osteosarcoma, the number of metastatic sites and whether they can be completely removed through surgery are factors that affect prognosis. So, starting appropriate treatment early for patients could effectively reduce tumor spread and increase survival time.