title: Proteomic profiling of heat shock protein 70 family members as biomarkers for hepatitis C virus-related hepatocellular carcinoma.
abstract: To identify proteins linked to the pathogenesis of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV), we profiled protein expression levels in samples of HCC. To identify essential proteins, ten samples of HCV-related HCC were analyzed by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. These experiments revealed increased levels of nine proteins in cancerous tissues compared to levels in corresponding noncancerous liver tissues. We focused on four members of the heat shock protein 70 family: 78 kDa glucose-regulated protein (GRP78), heat shock cognate 71 kDa protein (HSC70), 75 kDa glucose-regulated protein (GRP75), and heat shock 70 kDa protein 1 (HSP70.1). These results were confirmed by immunoblot analysis. In an additional 11 samples, the same expression patterns of these four proteins were observed. In total, 21 samples showed statistically significant up-regulation of GRP78, GRP75 and HSP70.1 in cancerous tissues. HSC70 showed a tendency toward overexpression. There has been no report describing overexpression of these four proteins simultaneously in HBV-related HCC as well as nonviral HCC. Our results suggest that these four proteins play important roles in the pathogenesis of HCV-related HCC and could be molecular targets for diagnosis and treatment of this disease.
authors.affiliation: Department of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Abe, Yamaguchi 755-8505, Japan.
authors.forename: Motonari
authors.initials: M
authors.lastname: Takashima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuramitsu
authors.forename: Yuuichiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Norio
authors.initials: N
authors.lastname: Iizuka
authors.forename: Toshifusa
authors.initials: T
authors.lastname: Toda
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Okita
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins