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Nuclear Matrix Protein Alterations Associated with Colon Cancer Metastasis to the Liver¹

Department of Urology [B. N. V., R. H. G.], and Department of Medicine, Division of Gastroenterology [G. B., R. E. S., A. J. B.], University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15232

Purpose: 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.

Experimental Design: 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.

Results: 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.

Conclusion: 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.

Commentary

Nuclear Matrix Proteins as Proteomic Markers of Preneoplastic and Cancer Lesions : Commentary re: G. Brunagel et al., Nuclear Matrix Protein Alterations Associated with Colon Cancer Metastasis to the Liver. Clin. Cancer Res., 8: 3039–3045, 2002.

Donald S. Coffey
Clin. Cancer Res. 2002 8: 3031-3033. [Full Text] [PDF]