Glycomic Analysis Distinguishes Gastric Cancer from Diseases with Similar Symptoms

Analysis of complex sugars (glycans) in serum samples enabled diagnosticians to distinguish patients with gastric cancer from those with gastritis or duodenal ulcers.

While gastric cancer is usually treatable when caught early, symptoms are indistinct and late detection leads to high mortality. The five-year survival rate of patients with gastric cancer in the United States is only 26.9%.

Investigators at the University of California, Davis (USA) used advanced glycomic techniques to distinguish patients with gastric cancer from those with diseases with similar overt symptoms (gastritis and duodenal ulcers). Glycomics is the comprehensive study of an organism's entire complement of sugars, whether free, or present in more complex molecules.

The investigators analyzed 72 serum samples collected from patients in Mexico City that presented with gastric cancer, gastritis, or duodenal ulcers. N-glycans were released from serum samples using a generic method based on the enzyme PNGase F (peptide -N-glycosidase F), an amidase that cleaves between the innermost N-acetyl-glucose and asparagine residues of high mannose, hybrid, and complex oligosaccharides from N-linked glycoproteins. Isolated glycans were characterized by MALDI FTICR MS.

Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique used in mass spectrometry, allowing the analysis of biomolecules (biopolymers such as DNA, proteins, peptides, and sugars) and large organic molecules (such as polymers, dendrimers, and other macromolecules), which tend to be fragile and fragment when ionized by more conventional ionization methods. Fourier transform ion cyclotron resonance (FTICR) mass spectrometry is a very high-resolution technique that can be used to determine masses with great accuracy. Many applications of FTICR-MS use this mass accuracy to help determine the composition of molecules based on accurate mass. FTICR-MS differs significantly from other mass spectrometry techniques in that the ions are not detected by hitting a detector such as an electron multiplier but only by passing near detection plates.

Results revealed that nineteen glycans were significantly different among the diagnostic groups. Generally, decreased levels of high-mannose type glycans, glycans with one complex type antenna, bigalactosylated biantennary glycans, and increased levels of non-galactosylated biantennary glycans were observed in gastric cancer cases. Altered levels of serum glycans were also observed in duodenal ulcers, but differences were generally in the same direction as in gastric cancer.

“We showed statistically significant differences between the serum glycan profiles of patients with gastric cancer and those with gastritis,” said senior author Dr. Jay Solnick, professor of comparative medicine at the University of California, Davis. “This is the first time anyone has looked at whether serum glycans could be used to detect gastric cancer. Right now, we have statistical significance but not predictive value. If we can improve the predictability, we could create a diagnostic test with real clinical value.”

The study was published in the December 10, 2013, online edition of the journal Cancer Prevention Research.

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