title: Autoantibodies against glucose-regulated protein 78 as serological biomarkers in metastatic and recurrent hepatocellular carcinoma.
abstract: OBJECTIVE
  To identify Heptocellular carcinoma (HCC) associated antigens by proteomics, and validate whether autoantibodies against tumor-associated antigens (TAAs) could be used for diagnosis and conditional monitoring.
  
  
  RESULTS
  The 78 kDa glucose regulated protein (GRP78) was selected as a candidate TAA. The titers of autoantibodies against 78 kDa glucose regulated protein (GRP78) from patients with HCC, liver cirrhosis (LC), and chronic hepatitis (CH) were significantly higher than that from normal controls (P<0.05, P<0.001, and P<0.01, respectively). The expression of autoantibodies against GRP78 was associated with clinical stage (P<0.01), portal vein invasion (P<0.05), and metastasis (P<0.05). The expression of anti-GRP78 antibodies was significantly higher 1 month after surgery in recurrent patients who had accepted hepatic resection 1 month after surgery compared to patients who had surgery before surgery or within 1 week after surgery (P<0.01 and P<0.001). Immunohistochemistry (IHC) showed higher expression of GRP78 in HCC compared to the non-HCC liver tissues (P <0.05).
  
  
  METHODS
  HCC serum with high titer of autoantibodies against TAAs were screened and used for a proteome-based approach to identify HCC associated antigens. Indirect enzyme-linked immunoassay (ELISA) was used to detect the corresponding autoantibodies against TAAs.
  
  
  CONCLUSIONS
  GRP78 is an autoantigen that could stimulate autoimmune responses and serve as a potential marker for recurrent and metastatic progression in HCC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.|Department of Gynecological Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ying
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Han
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: He
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Cong-Ya
authors.initials: CY
authors.lastname: Zhou
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Dong
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Meng-Jiao
authors.initials: MJ
authors.lastname: Cai
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sui
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Cheng-Xian
authors.initials: CX
authors.lastname: Ma
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Gou
authors.affiliation: Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, Kansas, USA.
authors.forename: Clifford
authors.initials: C
authors.lastname: Mason
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University Medical College, Xi'an, Shannxi, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000097:blood / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D045325:HCT116 Cells; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins
keywords: autoantibodies; biomarker; heptocellular carcinoma (HCC); proteomics; tumor associated antigens (TAA)