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Tissue and serum IGFBP7 protein as biomarker in high-grade soft tissue sarcoma
Maria Serena Benassi1, Laura Pazzaglia1, Chiara Novello1
1Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli Bologna, Italy.
Abstract:
Soft-tissue sarcomas (STS) are a heterogeneous group of mesenchymal tumors whose classification and treatment is complicated by molecular heterogeneity within the histological subtypes and by the lack of prognostic/therapeutic biomarkers. This study analyses expression of target proteins involved in insulin-like growth factor pathway (IGF1Rβ, IRS1 S612 and IGFBP7) in high-grade STS to stratify patients with the worst prognosis. Tissue microarray analysis performed on 145 high-grade STS samples revealed a uniform expression of IGF1Rβ and IRS1 S612, while IGFBP7 was more strongly expressed in metastatic than in metastasis-free patients. This was confirmed by multivariate regression analysis that demonstrated the independent poor prognostic role of IGFBP7 overexpression with a significant increase of risk of metastasis (HR = 6.358, 95% CI = 2.946-13.721; P < 0.0005). Given the evidence that circulating protein may generate from tissue tumor cells, in 59/145 patients who had available serum we measured IGFBP7 concentration. The ELISA assay revealed significantly higher levels in tumor patients than in the control with a possible threshold value of 25 ng/ml. Differentiating sera according to primary tumor histotype, significantly higher IGFBP7 concentration was found in synovial sarcoma and liposarcoma than in other STS histotypes. This study revealed that tissue expression of IGFBP7, considered a tumor stroma marker in mesenchymal derived cells, was highly prognostic in poor metastasis-free survival. In parallel, the determination of serum protein levels might contribute to STS diagnosis. Subsequent analyses will be crucial to understand the clinical relevance of IGFBP7 protein in STS.
Insights
Insulin-like growth factor binding protein 7 (IGFBP7) overexpression in soft-tissue sarcomas (STS) indicates a poor prognosis and increased metastasis risk. Serum IGFBP7 levels may aid in STS diagnosis and stratification.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Soft-tissue sarcomas (STS) are complex mesenchymal tumors with significant molecular heterogeneity.
- Lack of reliable prognostic and therapeutic biomarkers complicates STS classification and treatment.
- The insulin-like growth factor pathway is implicated in various cancers.
Purpose of the Study:
- To investigate the prognostic role of specific proteins in the insulin-like growth factor pathway in high-grade STS.
- To evaluate IGF1Rβ, IRS1 S612, and IGFBP7 as potential biomarkers for patient stratification.
- To correlate tissue and serum levels of IGFBP7 with STS prognosis and metastasis.
Main Methods:
- Tissue microarray analysis of 145 high-grade STS samples.
- Multivariate regression analysis to assess prognostic significance.
- Enzyme-linked immunosorbent assay (ELISA) to measure serum IGFBP7 concentrations in 59 patients.
- Comparison of IGFBP7 levels between STS patients and healthy controls, and across different STS histotypes.
Main Results:
- IGF1Rβ and IRS1 S612 showed uniform expression.
- IGFBP7 expression was significantly higher in metastatic STS compared to metastasis-free cases.
- IGFBP7 overexpression independently predicted poor metastasis-free survival (HR = 6.358, P < 0.0005).
- Serum IGFBP7 levels were significantly elevated in STS patients, with a potential diagnostic threshold of 25 ng/ml.
- Higher serum IGFBP7 concentrations were observed in synovial sarcoma and liposarcoma.
Conclusions:
- Tissue expression of IGFBP7 is a strong prognostic indicator for poor metastasis-free survival in high-grade STS.
- Serum IGFBP7 levels show potential for aiding in STS diagnosis and histotype differentiation.
- Further research is needed to elucidate the full clinical relevance of IGFBP7 in STS management.
