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

Abstract

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.

Article highlights

• The expression of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) exhibited a significant positive correlation in tumor tissues.

• A notable disparity was observed in the expression of CD44v6, CD44v6 and lung metastasis.

• Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival.

• When considering the combined expression of CD44v6 and MMP2, the double negative group for CD44v6 and MMP2 exhibited the most favorable 3-year metastasis-free survival (82.4%) and overall survival (85.7%) rates.

• Further multivariate analysis determined that co-expression of CD44v6 and MMP2 remained the most significant and independent prognostic factors for poor survival.

• The combined utilization of CD44v6 and MMP2 receiver operating characteristic analyses demonstrated a noteworthy area under the curve value of 0.817, signifying that the predictive efficacy of these two proteins exhibited an additive effect.

Keywords: :

• CD44v6
• metastasis
• MMP2
• osteosarcoma
• survival

Financial disclosure

This study was supported by Health Commission of Hebei Province, China. (Grant No. 20241625). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained institutional review board approval and have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, written informed consent was obtained from all patients and/or their legal guardian. The study protocol was approved by the Ethics Committee of the Second Hospital of Tangshan, China (Approve Number: 2023-17).

Data availability statement

The data used in this study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by Health Commission of Hebei Province, China. (Grant No. 20241625).