Tumor beta-1,4-galactosyltransferase IV overexpression is closely associated with colorectal cancer metastasis and poor prognosis.
OBJECTIVE
To elucidate the significance of beta-1,4-galactosyltransferase IV (beta-1,4-GT-IV) in the clinical presentation and prognostication of colorectal cancer.


METHODS
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).


CONCLUSIONS
Increased beta-1,4-GT-IV expression in tumor tissue was strongly associated with tumor metastases and poor prognosis in colorectal cancer.
Chen
Wei-Shone
WS
National Cancer Research Center, National Health Research Institutes, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University, Taiwan, Republic of China.
Chang
Hong-Yi
HY
Li
Chung-Pin
CP
Liu
Jacqueline Ming
JM
Huang
Tze-Sing
TS
D000368:Aged; D002232:Carbocyanines / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000201:enzymology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005700:Galactosyltransferases / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation
D002232:Carbocyanines; C089187:cyanine dye 3; C085321:cyanine dye 5; D005700:Galactosyltransferases; C111678:beta-1,4-galactosyltransferase IV