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Tumor ß-1,4-Galactosyltransferase IV Overexpression Is Closely Associated with Colorectal Cancer Metastasis and Poor Prognosis

Authors' Affiliations: ¹ National Cancer Research Center, National Health Research Institutes; ² Division of Colon and Rectal Surgery, Department of Surgery, ³ Division of Gastroenterology, Department of Medicine, and ⁴ Division of Experimental Surgery, Taipei Veterans General Hospital; and ⁵ National Yang-Ming University, Taipei, Taiwan, Republic of China

Requests for reprints: Tze-Sing Huang, National Cancer Research Center, National Health Research Institutes, 7th Floor, No. 161, Min-Chuan East Road Section 6, Taipei 114, Taiwan, Republic of China. Phone: 886-2-26534401, ext. 25138; Fax: 886-2-27929654; E-mail: tshuang{at}nhri.org.tw.

Purpose: To elucidate the significance of ß-1,4-galactosyltransferase IV (ß-1,4-GT-IV) in the clinical presentation and prognostication of colorectal cancer.

Experimental Design: Tissue lysates from paired tumor and nontumor tissues of a colon cancer patient were labeled separately with fluorescent dyes Cy5 and Cy3 for two-dimensional difference in-gel electrophoresis. Subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and immunoblot analyses identified a down-regulated level of ß-1,4-GT-IV in the tumor tissue. In the follow-up study, paired tissue lysates were obtained from 100 colorectal cancer patients with immunoblot analyses done to compare the levels of ß-1,4-GT-IV expression in these patients.

Results: Of 100 colorectal patients studied, 48% had down-regulated expression of ß-1,4-GT-IV in the tumor tissue but 28% of patients exhibited elevated ß-1,4-GT-IV levels. Increased ß-1,4-GT-IV in the tumor tissue was significantly coexistent with raised serum level of CA-199 and the presence of tumor metastasis (P = 0.006 and P < 0.001, respectively) but was independent of age and gender of patient, tumor site, tumor size, serum level of carcinoembryonic antigen, grade of tumor cell differentiation, and depth of tumor invasion. The results of logistic regression analyses suggested that tumor ß-1,4-GT-IV overexpression and tumor invasion, but not other patient variables such as tumor size and serum levels of carcinoembryonic antigen and CA19-9, were significantly correlated with the occurrence of metastases (P < 0.05). In a multivariate regression analysis, the patient group with tumor ß-1,4-GT-IV overexpression strongly predicted for tumor metastasis (odds ratio, 10.009; 95% confidence interval, 2.992-33.484; P < 0.001). Likewise, tumor ß-1,4-GT-IV overexpression was significantly associated with poor overall survival (P < 0.01). By Cox regression analysis, this association remained significant even after adjustment for tumor metastasis (P = 0.048).

Conclusion: Increased ß-1,4-GT-IV expression in tumor tissue was strongly associated with tumor metastases and poor prognosis in colorectal cancer.