Matrix metalloproteinase 9 (MMP-9) in osteosarcoma: Review and meta-analysis

Highlights

• Determine the diagnostic value of MMP-9 in detecting osteosarcoma by meta-analysis

• Pooled sensitivity and specificity were 0.78 and 0.90, respectively

• The assay kit subgroup is the main source of the heterogeneity

• MMP-9 is a potential biomarker for the diagnosis of OS

Abstract

The aim of this study is to determine the value of matrix metalloproteinase 9 (MMP-9) in diagnosis of osteosarcoma (OS). A systematic review and meta-analysis was conducted using MEDLINE, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, China Biomedical literature Database (CBM) and China National Knowledge Internet (CNKI) from inception through Aug 29, 2013. Articles written in English or Chinese that investigated the accuracy of MMP-9 for the diagnosis of OS were included. Pooled sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were determined. I² was used to test heterogeneity and source of heterogeneity was investigated by meta-regression (tested with Meta-DiSc and STATA 12.0 statistical softwares). A total of 3729 articles were retrieved, of which 18 were included, accounting for 892 patients. Overall, the pooled sensitivity, specificity and AUC were 0.78 (95% CI 0.730–0.83), 0.90 (95% CI 0.79–0.95), and 0.87 (95% CI 0.83–0.89), respectively. The studies had substantial heterogeneity (I² = 84%, 95% CI 65–100) (96%, 95% CI 94–99). Assay kit subgroup was the main source of the heterogeneity. Although MMP-9 was identified as a potential biomarker for OS, more studies were clearly needed to establish its diagnostic value.

Introduction

Osteosarcoma (OS) is a class of malignancy originating from the bone that mainly afflicts children or young adults. It is the second highest cause of cancer-related death in these age groups due to development of often fatal metastasis, usually in the lungs [1]. While OS can arise in any bone, the most common sites of primary tumors are the distal femur, proximal tibia and proximal humerus [2]. Typical signs and symptoms include history of pain, followed by localized swelling and limitations of joint movement and typical findings on X-rays. Plain radiographic films are usually the first diagnostic imaging study undertaken and should include the entire affected bone [3]. The classical appearance of OS on plain films shows destruction of the normal trabecular bone with presence of a Codman's Triangle formed by new periosteal formation and elevation of the cortex [4]. CT and MRI scanning are used to delineate the extent of the primary tumor and planning of definitive surgery [1]. Even though radiographic imaging is highly suggestive, tissue biopsy of OS must be obtained to confirm the diagnosis, which is generally obtained by open biopsy [5]. Laboratory evaluation is generally normal. However, serum alkaline phosphatase and lactate dehydrogenase levels have been reported elevated in 30%–40% of patients and have been associated with a poorer prognosis [1], [4].

Biomarkers are used as tools in cancer diagnostics and in treatment stratification [6]. In most cancers, there are increased levels of one or several members of the matrix metalloproteinases (MMPs), which could serve as diagnostic markers in cancer patients [7]. MMPs are a family of zinc- and calcium-dependent proteolytic enzymes. This is a family of proteolytic enzymes that are involved in many phases of cancer progression, including angiogenesis, invasiveness, and metastasis. In a study of colorectal cancer (CRC), MMP-9 showed a sensitivity of up to 99% and a specificity of 63% [8]. There are also studies showing that the presence of MMP-2 and MMP-9 can be a valuable predictor of bladder and prostate cancers [9], [10]. The aim of this report is to evaluate the diagnostic value of MMP-9 in the detection of OS, with the purpose to guide the clinical diagnosis.