Yang Yan-Hong, Deng Hua, Li Wen-Mei, Zhang Qing-Yun, Hu Xiao-Ting, Xiao Bai, Zhu Hai-Hong, Geng Pai-Li, Lu You-Yong
Laboratory of Molecular Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, PR China.
Clin Cancer Res. 2008 Jan 1;14(1):74-81. doi: 10.1158/1078-0432.CCR-07-1179.
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.
预后标志物的发现是人类癌症早期诊断和个体化治疗的一种策略。在本研究中，我们致力于整合不同方法以鉴定特定生物标志物并阐明其临床意义。
应用一种名为在线数字基因表达谱分析的强大工具来分离与胃癌相关的差异表达基因。分别通过半定量PCR、免疫组织化学染色和ELISA技术，在10种细胞系、123例肿瘤组织及305例胃癌血清标本中，对基质金属蛋白酶11（MMP11）进行mRNA和蛋白水平的筛选及验证。
我们的数据显示，与配对的正常组织相比，在细胞系和原发性肿瘤中持续检测到MMP11在mRNA和蛋白水平的过表达。重要的是，与对照组相比，胃癌患者血清MMP11水平也显著升高（P < 0.001），且阳性表达与胃癌患者的转移密切相关（P = 0.009）。此外，我们还表明MMP11的过表达与AGS细胞的恶性增殖有关。
基因表达谱分析与特定临床资源相结合是验证与恶性表型相关基因表达模式的一种有前景的方法。作为一种分泌蛋白，MMP11可能在致癌过程中起重要作用，并且作为包括胃癌在内的人类癌症诊断和预后的生物标志物具有潜在意义。
