title: The association of HMGB1 expression with clinicopathological significance and prognosis in hepatocellular carcinoma: a meta-analysis and literature review.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is the fifth most common cancer, and it is the second most common cancer-related mortality globally. The prognostic value of high mobility group box 1 (HMGB1) remains controversial. The purpose of this study is to conduct a meta-analysis and literature review to evaluate the association of HMGB1 expression with the prognosis of patients with HCC.
  
  
  METHODS
  A detailed literature search was made in Medline, Google Scholar and others for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, Hazard Ratio (HR) and mean difference with corresponding confidence intervals (CIs) were calculated and summarized respectively.
  
  
  RESULTS
  10 relevant articles were included for this meta-analysis study. HMGB1 mRNA levels in HCC were significantly higher than those in normal (p<0.00001) and para-tumor tissues (p = 0.002) respectively. The protein levels of HMGB1 in HCC were significantly higher than those in para-tumor tissues (p = 0.005). Two studies reported the serum HMGB1 levels in patients with HCC of TNM stages, and indicating significantly different between stage I and II, stage II and III, as well as stage III and IV (two studies showed p<0.01 and p<0.001 respectively). The overall survival (OS) was significantly shorter in HCC patients with high HMGB1 expression compared those with low HMGB1 expression and the pooled HR was 1.31 with 95% CI 1.20-1.44, Z = 5.82, p<0.0001. Two additional studies showed that there were higher serum HMGB1 levels in patients with chronic hepatitis than those in healthy people (p<0.05).
  
  
  CONCLUSIONS
  The results of this meta-analysis suggest that HMGB1 mRNA and protein tissue levels in the patients with HCC are significantly higher than those in para-tumor and normal liver tissues respectively. Tissue HMGB1 overexpression is a potential biomarker for HCC diagnosis, and it is significantly associated with the prognosis of patients with HCC.
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, School of Medicine and life Science, University of Jinan-Shandong Academy of Medical Science, Jinan, Shandong, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cancer Interventional Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cancer Interventional Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Cancer Interventional Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cancer Interventional Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Cancer Interventional Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Yinfa
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Xiugui
authors.initials: X
authors.lastname: Sheng
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, P.R. China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016239:MEDLINE; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009367:Neoplasm Staging; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D009363:Neoplasm Proteins