Abstract
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. 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. 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. 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.
Highlights
Prognostic markers discovery is a strategy for early diagnosis and individualization therapy for human cancer
Frequent overexpression of Matrix metalloproteinase 11 (MMP11) was determined in gastric cancer, and we investigated the expression status of MMP11 at both mRNA and protein level to validate the result of electronic expression profiling
MMP11 was selected as a cancer-related protein and its overexpression was consistently confirmed at both mRNA and protein level in cell lines and primary tumors of gastric cancer compared with matched normal tissues
Summary
Prognostic markers discovery is a strategy for early diagnosis and individualization therapy for human 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. Digital gene expression display (DGED) is a tool that compares gene expression between two pools of libraries It evaluates the statistical significance of the differences using the sequence odds ratio and a Bayesian test. MMP11 differs from other MMPs that are expressed as proenzymes and processed to active forms through proteolytic cleavage activated extracellularly, indicating that MMP11 may have a unique role in tumor development and progression [11] Based on this hypothesis, we have integrated gene expression profiling, tissue microarray, and regular laboratory analysis to validate MMP11 as a biomarker for cancer development and progression
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