Brünagel Gisela, Schoen Robert E, Bauer Anthony J, Vietmeier Barbara N, Getzenberg Robert H
Department of Medicine, Division of Gastroenterology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232, USA.
Clin Cancer Res. 2002 Oct;8(10):3039-45.
The development of colon cancer markers that can detect liver metastases early and predict which patients are at risk to develop liver metastases would have a major impact on this disease. We have previously identified G. Brunagel, et al., Cancer Research, 62:2437-2442, 2002, nuclear matrix proteins (NMPs), which are associated with colon cancer. The objective of this study is to identify the existence of a specific NMP "fingerprint" for human liver metastasis from colon cancer.
Using high-resolution two-dimensional gel electrophoresis, we analyzed the NMP expression of 12 matched liver metastases and adjacent normal samples and three normal donor liver samples. These were compared with colon cancer NMP patterns, along with several primary cell systems and lines.
Analysis of multiple gels for each sample revealed three proteins present in all liver metastases, which are not present in normal liver tissue and normal hepatocytes. These three proteins were also present in colon cancer samples.
Data provided here demonstrate that the NMP composition is able to differentiate liver metastases from normal liver tissue and normal hepatocytes and that these proteins are also expressed in colon cancer. These results further show that the adjacent normal liver tissue changes its NMP pattern of expression. Development of an assay to detect these specific NMPs in tissue and/or serum specimens is a promising modality for early detection of liver metastases from colon cancer or potentially as a prognostic tool. In addition the functional characterization of these proteins will significantly enhance our understanding of the development of liver metastases of this disease.
开发能够早期检测结肠癌肝转移并预测哪些患者有发生肝转移风险的标志物，将对这种疾病产生重大影响。我们之前已鉴定出与结肠癌相关的核基质蛋白（NMPs）（G. Brunagel等人，《癌症研究》，62:2437 - 2442，2002年）。本研究的目的是确定结肠癌肝转移是否存在特定的NMP“指纹”。
我们使用高分辨率二维凝胶电泳分析了12对匹配的肝转移灶和相邻正常样本以及3个正常供体肝脏样本的NMP表达情况。将这些样本与结肠癌NMP模式以及几个原代细胞系进行了比较。
对每个样本的多张凝胶进行分析后发现，所有肝转移灶中均存在三种蛋白质，而正常肝组织和正常肝细胞中不存在这些蛋白质。这三种蛋白质在结肠癌样本中也存在。
此处提供的数据表明，NMP组成能够区分肝转移灶与正常肝组织和正常肝细胞，并且这些蛋白质在结肠癌中也有表达。这些结果进一步表明，相邻的正常肝组织会改变其NMP表达模式。开发一种检测组织和/或血清样本中这些特定NMP的检测方法，有望用于早期检测结肠癌肝转移或作为一种潜在的预后工具。此外，对这些蛋白质的功能特性进行表征将显著增进我们对该疾病肝转移发生发展的理解。
