Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers
Tumour matrilysin expression predicts metastatic potential of stage I (pT1) colon and rectal cancers
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DOI：
10.1136/gut.2005.071035
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发表时间：
2005-12-01
期刊：
影响因子：
24.5
通讯作者：
Imai, K
中科院分区：
文献类型：
--
作者：
Kurokawa, S;Arimura, Y;Imai, K
背景和目的：结转移是结肠癌和直肠癌预后的决定因素。使用经典的组织学标准，许多预测淋巴结转移的尝试都失败了，阻止了I期（pT1）癌症的充分管理。我们研究了肿瘤基质溶解素在预测转移潜能中的作用，并讨论了其在PT1结肠和直肠cancer.Methods的个体化治疗中的潜在用途：通过cDNA阵列研究了24例结肠和直肠癌中与淋巴结转移相关的基因特征。我们研究了494例结肠癌和直肠癌患者，以确定淋巴结转移的危险因素，并通过logistic回归模型或内置matrilysin的贝叶斯神经网络模型评估预测淋巴结转移的潜力。然后，我们推断可能的因果关系的结转移的结构方程modeling.Results：cDNA阵列显示，基质溶解素是最大的上调转移签名确定。肿瘤基质溶解素的表达作为一个阶段独立的风险因素，淋巴结转移，在两个模型中的受试者工作特征曲线分析的预测性能相似。一种称为自动相关性确定的贝叶斯方法将基质溶解素确定为最相关的预测因子之一。结构方程模型表明matrilysin和nodal metastasis.Conclusions之间可能存在直接的因果关系：我们提供了证据表明，肿瘤matrilysin的表达是一个很有前途的生物标志物预测结直肠癌的结转移。肿瘤基质溶解素表达的分析将有助于临床医生实现基于pT1结肠癌和直肠癌转移潜力的个体化癌症治疗的目标。
Background and aims: Nodal metastases are indisputable determinants of prognosis for colon and rectal cancer. Using classical histological criteria, many attempts to predict nodal metastasis have failed, preventing the adequate management of stage I (pT1) cancer. We investigated the role of tumour matrilysin in predicting metastatic potential, and discuss its potential use in individualising treatment of pT1 colon and rectal cancer.Methods: The gene signature associated with nodal metastasis was investigated by cDNA array in 24 colon and rectal cancers. We studied 494 colon and rectal cancer patients to identify risk factors for nodal metastasis and evaluated the potential to predict nodal metastasis by either the logistic regression model or the Bayesian neural network model with built-in matrilysin. We then inferred possible causality of nodal metastasis from structural equation modelling.Results: cDNA array revealed that matrilysin was maximally upregulated in the metastasis signature identified. Tumour matrilysin expression emerged as a stage independent risk factor for nodal metastasis, resulting in a similar predictive performance in receiver operating characteristic curve analysis in the two models. A Bayesian approach called automatic relevance determination identified matrilysin as one of the most relevant predictors examined. Structural equation modelling suggested possible direct causality between matrilysin and nodal metastasis.Conclusions: We have provided evidence that tumour matrilysin expression is a promising biomarker predicting nodal metastasis of colon and rectal cancer. Analysis of tumour matrilysin expression would help clinicians achieve the goal of individualised cancer treatment based on the metastatic potential of pT1 colon and rectal cancer.