Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma.
Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma.
复制标题
DOI：
--
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Hiroki Kuniyasu;Lee M. Ellis;D. Evans;J. Abbruzzese;C. Fenoglio;C. Bucana;Karen R. Cleary;Eiichi Tahara;I. Fidler
中科院分区：
文献类型：
--
作者：
Hiroki Kuniyasu;Lee M. Ellis;D. Evans;J. Abbruzzese;C. Fenoglio;C. Bucana;Karen R. Cleary;Eiichi Tahara;I. Fidler
我们研究了几个基因的表达水平，调节不同的步骤转移福尔马林固定，石蜡包埋，档案标本的原发性人胰腺癌患者接受根治性手术。通过比色原位mRNA杂交技术检测表皮生长因子受体、E-钙粘蛋白、IV型胶原酶（基质金属蛋白酶（MMP）2和MMP-9）、碱性成纤维细胞生长因子、血管内皮生长因子/血管通透性因子和白细胞介素8的表达。肿瘤周围E-钙粘蛋白的下调和IV型胶原酶（MMP-9和MMP-2）的上调（分别为P = 0.0167、0.0102和0.0349）具有显著的预后价值。复发患者肿瘤周围IV型胶原酶表达（MMP-2和MMP-9表达的平均值）与E-钙粘蛋白表达的比值（MMP：E-钙粘蛋白比值）（4.7 ± 2.1）显著高于无复发患者（2.3 ± 1.7; P = 0.0008）。总生存分析显示，胰腺癌死亡与高MMP：E-cadherin比值（>3.0）显著相关（P < 0.0002），而术后28-64个月存活的8例患者中有7例MMP：E-cadherin比值较低（<3.0）。总生存率的多因素分析显示MMP：E-cadherin比值是一个重要的独立预后因素，而分期、淋巴结转移和组织学类型则不是。这些数据表明，多参数分析的几个转移相关基因可能允许医生评估转移的潜力，从而预测个体患者的临床结果与可切除的胰腺癌。
We examined the expression level of several genes that regulate distinct steps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative surgery. The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybridization technique. Down-regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patients alive 28-64 months after surgery. Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, whereas stage, nodal metastasis, and histological type were not. These data show that multiparametric analysis for several metastasis-related genes may allow physicians to assess the metastatic potential and hence predict the clinical outcome of individual patients with resectable pancreatic carcinoma.