Clinical utility of quantitative RT-PCR targeted to α1,4-N-acetylglucosaminyltransferase mRNA for detection of pancreatic cancer

alpha,4-N-Acetylglucosaminyltransferase (alpha 4GnT) is a glycosyltransferase responsible for the biosynthesis of alpha 1,4-GlcNAc-capped O-glycans, and is frequently expressed in pancreatic cancer cells but not peripheral blood cells. In the present study, we tested the clinical utility of a4GnT mRNA expressed in the mononuclear cell fraction of peripheral blood as a biomarker of pancreatic cancer. Total RNA isolated from the peripheral blood mononuclear cells from 55 pancreatic cancer patients, 10 chronic pancreatitis patients, and 70 cancer-free volunteers was analyzed quantitatively by reverse transcription-polymerase chain reaction with primers specific for alpha 4GnT, and the expression level of a4GnT mRNIA relative to that of glyceralclehyde-3-phosphate dehydrogenase (GAPDH) was measured. When the ratio of a4GnT to GAPDH transcripts exceeded a defined cut-off value, patients were considered to have pancreatic cancer. By these standards, 76.4% of the pancreatic cancer patients were detected by this assay. A strong correlation was obtained between positivity in this assay and the expression of a4GnT protein detected immunohistochemically in pancreatic cancer tissues resected subsequently, suggesting that a4GnT mRNA detected in the peripheral blood is derived from circulating pancreatic cancer cells. Although increased levels of alpha 4GnT mRINA was detected in 40.0% of chronic pancreatitis patients and 17.1% of cancer-free volunteers, the expression levels were significantly lower than those seen in pancreatic cancer patients. These results suggest that quantitative analysis of alpha 4GnT mRNA expressed in the mononuclear cell fraction of peripheral blood will contribute to the detection of pancreatic cancer.