Expression of CXCR4 and MMP-2 is associated with poor prognosis in patients with osteosarcoma

Histol Histopathol. 2020 Aug;35(8):863-870. doi: 10.14670/HH-18-219. Epub 2020 Apr 21.

Abstract

Background: Osteosarcoma is a primary malignant tumor with a high tendency to form metastasis and poor prognosis. Consequently, finding effective early indicators of metastases is crucial for identifying and treating high-risk patients. CXCR4 and MMP-2 have been found to strongly correlate with invasion and metastasis of malignant tumors, including osteosarcoma.

Materials and methods: Our study evaluated CXCR4 in conjunction with MMP-2 as an important clinicopathological prognostic predictor for metastasis and overall survival of osteosarcoma. 73 patients' clinical data and pathological samples were retrieved for the study. A median time of 36 months follow-up was performed to evaluate for tumor metastasis and patient survival. CXCR4 and MMP-2 proteins in tumor tissues were detected by immunohistochemistry on paraffin-embedded tissue sections.

Results: The positive expression rate of CXCR4 and MMP-2 was 68.5% and 54.8% respectively, and of the 45 patients who developed distal metastasis, 33 and 28 patients had positive expression of CXCR4 and MMP-2 respectively. The median metastasis-free survival was 72.00 months in the CXCR4-negative group and 14.00 months in the CXCR4 positive group. Furthermore, median overall survival was 73.77 and 24.00 months in these same two groups. Further, the median metastasis-free survival was 66.51 months in the MMP-2 negative group and 9.00 months in the MMP-2 positive group. The median overall survival was 75.07 and 19.00 months in these same two groups. MMP2 and metastasis remained the significant and independent prognostic factors for metastasis-free survival and overall survival by using the COX regression model adjusted for the multivariate predictors of survival.

Conclusion: Our results suggest that metastasis and MMP-2 are both independent prognostic indicators for metastasis-free and overall survival of osteosarcoma patients.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / pathology*
  • Child
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Middle Aged
  • Osteosarcoma / pathology*
  • Prognosis
  • Progression-Free Survival
  • Receptors, CXCR4 / biosynthesis*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CXCR4 protein, human
  • Receptors, CXCR4
  • MMP2 protein, human
  • Matrix Metalloproteinase 2