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Identification of Matrix Metalloproteinase 11 as a Predictive Tumor Marker in Serum Based on Gene Expression Profiling

Authors' Affiliations: ¹ Laboratory of Molecular Oncology; ² Department of Clinical Laboratory, Peking University School of Oncology, Beijing Cancer Hospital and Institute; ³ Basic Medical Research Center, Capital Medical University affiliated Beijing Chao-Yang Hospital, Beijing, P.R. China; and ⁴ Department of Immunology, Qinghai Medical College, Xining, P.R. China

Requests for reprints: You-Yong Lu, Laboratory of Molecular Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Fu-Cheng Road 52, Hai-Dian District, Beijing 100036, P.R. China. Phone: 86-10-88196765; Fax: 86-10-88122437; E-mail: yongylu{at}public.bta.net.cn.

Purpose: Prognostic markers discovery is a strategy for early diagnosis and individualization therapy for human cancer. In this study, we focus to integrate different methods to identify specific biomarker and elucidate its clinical significance.

Experimental Design: A powerful tool named Digital Gene Expression Display online was applied to isolate differentially expressed genes correlated with gastric cancer. Matrix metalloproteinase 11 (MMP11) was selected and confirmed at both mRNA and protein level in 10 cell lines, 123 cases of tumor tissues, and 305 cases of gastric cancer serum specimen by semiquantitative PCR, immunohistochemistry staining, and ELISA techniques, respectively.

Results: Our data showed that overexpression of MMP11 at mRNA and protein level was consistently detected in cell lines and primary tumors compared with matched normal tissues. Importantly, serum MMP11 levels were also significantly elevated in gastric cancer patients compared with those of the control subjects (P < 0.001), and the positive expression was well correlated with metastasis in gastric cancer patients (P = 0.009). Furthermore, we have shown that overexpression of MMP11 was associated with the malignant proliferation of AGS cells.

Conclusions: Combination of gene expression profiling and specific clinical resource is a promising approach to validate gene expression patterns associated with malignant phenotype. As a secreted protein, MMP11 may play an important role in carcinogenesis and has potential implication as a biomarker for the diagnosis and prognosis of human cancers including gastric cancer.

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