课题组前期研究发现胃癌患者胃液芳香族氨基酸（AAAs）含量异常升高，有望成为胃癌早期诊断的生物标志物，但机制未明。本研究拟从细胞外代谢入手，以IV型胶原为靶点，MMP-2/9为切入点，AAAs为代谢产物，解释上述现象出现的原因。具体步骤如下：首先，分别在人体组织和细胞层面明确MMP-2/9与AAAs间的相关性；然后，通过细胞干预实验证明人胃癌细胞可以通过MMP-2/9降解IV型胶原产生AAAs；最后，通过动物实验证实MMP-2/9对裸鼠皮下种植瘤组织生长与AAAs含量的影响。旨在为胃癌的早期诊断和筛查提供新方法和新思路，为胃液AAAs含量检测临床应用提供理论依据。

In the previous study, we found that the level of aromatic amino acids (AAAs) in gastric juice from gastric cancer patients was higher than non-neoplastic gastric disease patients, which is expected to become biomarkers for early detection of gastric cancer, but the underlying mechanism of this phenomenon is still not clear. In this study, we will clarify the role of proteolytic enzymes MMP-2 and MMP-9 in the difference of gastric juice AAAs content between gastric cancer, gastric dysplasia and chronic gastritis patients from extracellular metabolism primarily. Therefore, we put forward the scientific hypothesis that treating type IV collagen as target, MMP-2/9 as driving factor, AAAs as metabolic products. Specific steps are as follows: To begin with, the correlation between MMP-2/9 and AAAs was clearly defined at human tissue and cell level respectively. Secondly, it was proved that through knockdown or overexpression of MMP-2/9 gene in human gastric carcinoma cells, type IV collagen could be degraded more or less, result in the content of AAAs increase or decrease correspondingly. Finally, nude mouse transplantation tumor experiment was carried out to observe anti-tumor effects, initiating or promoting tumorigenesis and the change of AAAs content in transplanted tumor tissue of the mouse from RNA interference and gene overexpression. Above all, the ultimate goals of this project are to open a new approach for early diagnosis and screening of gastric malignancies, and to provide a theoretical basis for its clinical application.