title: Identification of novel serum biomarkers of hepatocellular carcinoma using glycomic analysis.
abstract: The altered N-glycosylation of glycoproteins has been suggested to play an important role in the behavior of malignant cells. Using glycomics technology, we attempted to determine the specific and detailed N-glycan profile for hepatocellular carcinoma (HCC) and investigate the prognostic capabilities. From 1999 to 2011, 369 patients underwent primary curative hepatectomy in our facility and were followed up for a median of 60.7 months. As normal controls, 26 living Japanese related liver transplantation donors were selected not infected by hepatitis B and C virus. Their mean age was 40.0 and 15 (57.7%) were male. We used a glycoblotting method to purify N-glycans from preoperative blood samples from this cohort (10 μL serum) which were then identified and quantified using mass spectrometry (MS). Correlations between the N-glycan levels and the clinicopathologic characteristics and outcomes for these patients were evaluated. Our analysis of the relative areas of all the sugar peaks identified by MS, totaling 67 N-glycans, revealed that a proportion had higher relative areas in the HCC cases compared with the normal controls. Fourteen of these molecules had an area under the curve of greater than 0.80. Analysis of the correlation between these 14 N-glycans and surgical outcomes by univariate and multivariate analysis identified G2890 (m/z value, 2890.052) as a significant recurrence factor and G3560 (m/z value, 3560.295) as a significant prognostic factor. G2890 and G3560 were found to be strongly correlated with tumor number, size, and vascular invasion.
  
  
  CONCLUSIONS
  Quantitative glycoblotting based on whole serum N-glycan profiling is an effective approach to screening for new biomarkers. The G2890 and G3560 N-glycans determined by tumor glycomics appear to be promising biomarkers for malignant behavior in HCCs. (HEPATOLOGY 2013;).
authors: Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan. t-kamiya@med.hokudai.ac.jp
authors: Toshiya
authors: T
authors: Kamiyama
authors: Hideki
authors: H
authors: Yokoo
authors: Jun-Ichi
authors: J
authors: Furukawa
authors: Masaki
authors: M
authors: Kurogochi
authors: Tomoaki
authors: T
authors: Togashi
authors: Nobuaki
authors: N
authors: Miura
authors: Kazuaki
authors: K
authors: Nakanishi
authors: Hirofumi
authors: H
authors: Kamachi
authors: Tatsuhiko
authors: T
authors: Kakisaka
authors: Yosuke
authors: Y
authors: Tsuruga
authors: Masato
authors: M
authors: Fujiyoshi
authors: Akinobu
authors: A
authors: Taketomi
authors: Shin-Ichiro
authors: S
authors: Nishimura
authors: Satoru
authors: S
authors: Todo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D016022:Case-Control Studies; D002423:Cause of Death; D018572:Disease-Free Survival; D005260:Female; D054794:Glycomics; D006498:Hepatectomy; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011134:Polysaccharides / Q000097:blood*; D012372:ROC Curve; D012008:Recurrence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011134:Polysaccharides