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Cystatin-like Metastasis-associated Protein mRNA Expression in Human Colorectal Cancer Is Associated with Both Liver Metastasis and Patient Survival ¹

Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu 874-0838 [T. U., A. K., M. Mori], and Banyu Tsukuba Research Institute in collaboration with Merck Research Laboratories, Ibaraki 300-2611 [Y. H., M. Morita, H. A., S. N.], Japan

Purpose and Experimental Design: We previously reported that an increased expression of cystatin-like metastasis-associated protein (CMAP) mRNA is involved in liver-specific metastasis in a mouse model. We also identified its human homologue and showed that the expression of CMAP in various human cancer cell lines correlated with the description of malignancy in these cell lines. However, there is still no information available on the clinical significance of CMAP expression in human cancer specimens. Thus, we studied the CMAP expression levels using a real-time quantitative reverse transcription-PCR for 79 patients with colorectal cancer, including 17 cases with liver metastasis.

Results: The mean expression level of CMAP in tumor tissue specimens was significantly higher than in the corresponding normal tissue specimens (P < 0.05). A higher expression of CMAP was significantly correlated with liver metastasis (P < 0.01) as well as with a less differentiated histological type (P < 0.05) of colorectal cancer. An increased expression of CMAP was also identified as the strongest independent factor for liver metastasis based on a multivariate analysis (P < 0.001). Furthermore, the prognosis of the patients with a higher expression of CMAP was significantly worse than those with a lower expression (5-year survival rate; 49.7% and 75.0%, respectively, P = 0.038).

Conclusions: These findings imply that the expression level of CMAP in human cancer may be a new biomarker for both liver metastasis and the patient’s outcome.

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