Abstract
ABSTRACT Objective S100A9 is a calcium- and zinc-binding molecule of S100 family. The aim of the study was to evaluate the role of S100A9 in osteosarcoma (OS) and its value as a diagnostic and therapeutic target in OS. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and microdissection-based mRNA analysis were used to detect S100A9 mRNA and protein expression in OS and normal bone tissues and its potential as a diagnostic marker in OS. In vitro experiments with RNA interference were performed to evaluate the functional role of S100A9 and its potential as a therapeutic target in OS. Results: S100A9 mRNA levels were significantly higher in OS tissues than that of in normal bone tissues. Receiver operating characteristic curves showed that S100A9 could be a useful diagnostic marker in OS. In vitro data showed that inhibition of S100A9 decreased the proliferation and invasiveness of OS cells, and these findings were supported by microarray data. Conclusions: Assessment of S100A9 mRNA expression is a promising tool for the diagnosis of OS, and S100A9 may be a promising therapeutic target in OS.
Highlights
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents
S100A9 mRNA levels were measured in 56 OS and 39 normal bone tissue samples. β-actin was used as a reference gene to quantify target gene expression (Figure 1(a))
To confirm that quantification of S100A9 mRNA is a valid method for differentiating OS from normal bone tissue, the expression of S100A9 mRNA and protein was compared between OS and normal bone tissues
Summary
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The 5-year survival of patients with localized OS remains at 60–70% after treatment with surgery and multiagent chemotherapy [1]. Up to 20–25% of the patients have detectable metastatic disease at the time of diagnosis [2]. Metastatic OS is associated with poor response to standard chemotherapy, resulting in poor prognosis. The lack of useful biomarkers is an important clinical problem in OS [3]. Despite recent advances in the treatment of OS, the clinical outcomes of OS patients have not substantially improved in over 30 years [4]. It is imperative to explore new prognostic indicators and novel therapeutic approaches for this disease once it has been detected
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