Tanabe Kazuhiro, Deguchi Akihiro, Higashi Mikito, Usuki Hisashi, Suzuki Yasuyuki, Uchimura Youichi, Kuriyama Shigeki, Ikenaka Kazuhiro
Analytical Services Division, Mitsubishi Chemical Group Science and Technology Research Center Inc.,1000 Kamoshida-cho, Aoba-ku, Yokohama-shi, Kanagawa 227-8502, Japan.
Biochem Biophys Res Commun. 2008 Sep 19;374(2):219-25. doi: 10.1016/j.bbrc.2008.06.124. Epub 2008 Jul 11.
Serum glycans are promising markers for early-stage cancer detection, but the research remains challenging because low concentrations of serum glycoproteins are secreted from early-stage tumors. We have established an N-glycan profiling method using liquid chromatography electrospray ionization-mass spectrometry with high sensitive derivative, trimethyl(4-aminophenyl)ammonium chloride (TMAPA). The mass sensitivity of TMAPA-labeled oligosaccharides was enhanced more than 50 times compared with 2-aminopyridine (PA) labeled oligosaccharides, and the analytical period was significantly shortened compared with traditional HPLC 2D-mapping. Using this method, we found about 28 major N-linked oligosaccharides in human sera, and we investigated their alterations in patients who developed hepatocellular carcinoma (HCC). We found that outer arm fucosylation (attached GlcNAc via an alpha 1-3/4 linkage) in highly branched oligosaccharides increased significantly in sera of HCC patients. Normalizing the level of outer arm fucosylation by taking into account platelet concentration allowed us to distinguish more clearly between HCC and LC patients.
