title: Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma.
abstract: Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (-) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (-) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (-) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (-) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets.
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Yuan-Quan
authors.initials: YQ
authors.lastname: Yu
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jia-Le
authors.initials: JL
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The Red Cross Hospital in Hangzhou, Hangzhou, Zhejiang, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Geng
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Qian
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhou
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Da-Ren
authors.initials: DR
authors.lastname: Liu
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Shu-You
authors.initials: SY
authors.lastname: Peng
authors.affiliation: Center for Cancer Research and Department of Biochemistry, Zhejiang University School of Basic Medical Sciences, Hangzhou, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
authors.forename: Jiang-Tao
authors.initials: JT
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000276:immunology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000276:immunology; D012372:ROC Curve; D012680:Sensitivity and Specificity; D025521:Tumor Suppressor Proteins / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: biomarker; diagnosis; hepatocellular carcinoma; microvascular invasion; sero-proteomics