Establishment of laboratory method using the expression of extracellular matrix components as markers for diagnosis and prognosis of cancer and inflammatory diseases

我们研究了基质金属蛋白酶（MMPs）和组织金属蛋白酶抑制剂（TIMP）以及细胞外基质成分（如层粘连蛋白和merosin）的表达是否与癌症和炎症性疾病等疾病的状态相关。我们发现血清MMP-9水平与胃肠道癌症（结肠癌和胰腺癌）的晚期疾病状态以及胃癌患者的预后相关。我们还发现脑脊液MMP-2和MMP-9水平与脑肿瘤（如胶质母细胞瘤）的恶性表型相关。我们建立了检测层粘连蛋白、MMP-2、MMP-9和TIMP mRNA表达的RT-PCR方法。我们还建立了层粘连蛋白亚基表达的原位杂交检测方法，并将该方法应用于人肝细胞癌中层粘连蛋白亚基的检测。肝细胞癌的分化与层粘连蛋白亚基的表达密切相关。

We have investigated whether the expression of matrix metalloproteases (MMPs) and tissue inhibitor of metalloprotease (TIMP), and of extracellular matrix components such as laminin, and merosin are associated with status of disease such as cancer and inflammatory diseases. We have found that serum MMP-9 level was associated with advanced disease status in gastrointestinal cancers (colon and pancreas cancer), and with prognosis of gastric cancer patients. We also found that CSF MMP-2 and MMP-9 levels were associated with malignant phenotype of brain tumor such as glioblastoma. We established RT-PCR method for measurements of laminin, MMP-2, MMP-9, and TIMP mRNA expression. We also established in situ hybridization method for detection of laminin subunit expression, and applied this method for the detection of laminin subunit in human hepatocellular carcinoma. Differentiation of hepatocellular carcinoma was intimately associated with expression of laminin subunits.