title: Global PROTOMAP profiling to search for biomarkers of early-recurrent hepatocellular carcinoma.
abstract: This study used global protein expression profiling to search for biomarkers to predict early recurrent hepatocellular carcinoma (HCC). HCC tissues surgically resected from patients with or without recurrence within 2 years (early recurrent) after surgery were compared with adjacent nontumor tissue and with normal liver tissue. We used the PROTOMAP strategy for comparative profiling, which integrates denaturing polyacrylamide gel electrophoresis migratory rates and high-resolution, semiquantitative mass-spectrometry-based identification of in-gel-digested tryptic peptides. PROTOMAP allows examination of global changes in the size, topography, and abundance of proteins in complex tissue samples. This approach identified 8438 unique proteins from 45 708 nonredundant peptides and generated a proteome-wide map of changes in expression and proteolytic events potentially induced by intrinsic apoptotic/necrotic pathways. In the early recurrent HCC tissue, 87 proteins were differentially expressed (≥20-fold) relative to the other tissues, 46 of which were up-regulated or specifically proteolyzed and 41 of which were down-regulated. This data set consisted of proteins that fell into various functional categories, including signal transduction and cell organization and, notably, the major catalytic pathways responsible for liver function, such as the urea cycle and detoxification metabolism. We found that aberrant proteolysis appeared to occur frequently during recurrence of HCC in several key signal transducers, including STAT1 and δ-catenin. Further investigation of these proteins will facilitate the development of novel clinical applications.
authors: Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University , Minamiosawa 1-1, Hachioji-shi, Tokyo 192-0397, Japan.
authors: Masato
authors: M
authors: Taoka
authors: Noriaki
authors: N
authors: Morofuji
authors: Yoshio
authors: Y
authors: Yamauchi
authors: Hidenori
authors: H
authors: Ojima
authors: Daisuke
authors: D
authors: Kubota
authors: Goro
authors: G
authors: Terukina
authors: Yuko
authors: Y
authors: Nobe
authors: Hiroshi
authors: H
authors: Nakayama
authors: Nobuhiro
authors: N
authors: Takahashi
authors: Tomoo
authors: T
authors: Kosuge
authors: Toshiaki
authors: T
authors: Isobe
authors: Tadashi
authors: T
authors: Kondo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis*; D058645:Denaturing Gradient Gel Electrophoresis; D004591:Electrophoresis, Polyacrylamide Gel; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000235:genetics; D011506:Proteins / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins
keywords: PROTOMAP; biomarker; hepatocellular carcinoma; mass spectrometry; proteomics