Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma.
Differential expression of E-cadherin and type IV collagenase genes predicts outcome in patients with stage I non-small cell lung carcinoma.
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发表时间：
2000-03
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通讯作者：
Roy S. Herbst;Seiji Yano;Hiroki Kuniyasu;F. Khuri;C. Bucana;Fang Guo;Diane Liu;Bonnie L. Kemp-Bonnie-L.-K
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作者：
Roy S. Herbst;Seiji Yano;Hiroki Kuniyasu;F. Khuri;C. Bucana;Fang Guo;Diane Liu;Bonnie L. Kemp-Bonnie-L.-K
由于原发性非小细胞肺癌的常规组织病理学检查不能预测疾病的结局，我们将疾病的结局与调节转移过程不同步骤的多个基因的表达水平相关联，这些基因来自于M. D.安德森癌症中心。通过比色原位mRNA杂交技术检测E-钙粘蛋白（与细胞凝聚相关）、IV型胶原酶[基质金属蛋白酶（MMP）-2和MMP-9，与侵袭相关]和三种血管生成分子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。通过考克斯单变量分析分析的单个基因的表达水平不具有预后性。相比之下，IV型胶原酶（MMP-2和MMP-9的平均表达）和E-钙粘蛋白的表达之间的比率，MMP：E-钙粘蛋白的比率（在每个肿瘤的周边测量），在复发性疾病的患者中显著高于保持无疾病的患者（P = 0.00003）。Kaplan-Meier生存分析显示，较长的总生存期和较低的疾病复发率与较低的MMP：E-cadherin比值（<2）显著相关（分别为P = 0.0002和P = 0.0001）。总生存期和无病生存期的多协变量分析也得出结论，MMP：E-cadherin比率是校正年龄后的重要预后因素（P = 0.0001）。因此，在个体人类肺癌中确定该基因表达比率可用于指导可切除肺癌个体患者的定制治疗。
Because routine histopathological examination of primary non-small cell lung cancer does not predict disease outcome, we correlated disease outcome with the expression level of multiple genes that regulate distinct steps of the metastatic process in 60 formalin-fixed, paraffin-embedded, archival specimens of stage I lung carcinoma from patients undergoing curative surgery at the M. D. Anderson Cancer Center. The expression of E-cadherin (related to cell cohesion), type IV collagenase [matrix metalloproteinase (MMP)-2 and MMP-9, related to invasion], and three angiogenic molecules, basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8, were examined by a colorimetric in situ mRNA hybridization technique. The expression levels of the individual genes analyzed by a Cox univariate analysis were not prognostic. In contrast, the ratio between expression of type IV collagenases (mean of the expression of MMP-2 and MMP-9) and E-cadherin, the MMP:E-cadherin ratio (measured at the periphery of each tumor), was significantly higher in patients with recurrent disease than in patients who remained disease free (P = 0.00003). Longer overall survival and reduced disease recurrence rates were significantly associated with a lower MMP:E-cadherin ratio (<2) by a Kaplan-Meier survival analysis (P = 0.0002 and P = 0.0001, respectively). Multiple covariate analyses of overall and disease-free survival also concluded that the MMP:E-cadherin ratio was a significant prognostic factor when corrected for age (P = 0.0001). Determination of this gene expression ratio in individual human lung cancers might therefore be used to direct tailored treatment for individual patients with resectable lung cancer.