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 beta-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 beta-1,4-GT-IV expression in these patients.
RESULTS: Of 100 colorectal patients studied, 48% had down-regulated expression of beta-1,4-GT-IV in the
tumor tissue but 28% of patients exhibited elevated beta-1,4-GT-IV levels. Increased beta-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 beta-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 beta-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 beta-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: