The association of HMGB1 expression with clinicopathological significance and prognosis in hepatocellular carcinoma: a meta-analysis and literature review.

Lu Zhang,Jianjun Han,Huiyong Wu,Jinming Yu,Jian Li,Yinfa Xie,Li Xie,Xiaohong Liang,Xiugui Sheng,Jianxin Zhang,Erica Villa

doi:10.1371/journal.pone.0110626

Lu Zhang, Jianjun Han + Show 9 more

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https://doi.org/10.1371/journal.pone.0110626

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Abstract

BackgroundHepatocellular 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.MethodsA 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.Results10 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).ConclusionsThe 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.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men, worldwide, and seventh among women, and it is the second leading cause of cancer-related mortality globally [1].HCC commonly occurs in Asia and Africa, and its incidence rate is starting to increase in Western countries [2,3]
Due to lack of effective biomarkers for diagnosis and prognosis, HCC is frequently found in late stages, when curative therapy approaches like resection, liver transplantation, radio frequency ablation (RFA), and transarterial chemoembolization (TACE) don’t produce satisfactory clinical outcomes
The effects of other biomarkers to predict the prognosis for HCC such as vascular endothelial growth factor (VEGF), Cyclin-dependent Kinases(CDK), b-catenin/Wnt pathway and microRNAs [15] have been controversial and again none of them has been applied to the clinical settings

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer in men, worldwide, and seventh among women, and it is the second leading cause of cancer-related mortality globally [1].HCC commonly occurs in Asia and Africa, and its incidence rate is starting to increase in Western countries [2,3]. The serum a-fetoprotein (AFP) has been widely used as a risk assessment factor in patients with cirrhosis and a screening method for early detection of HCC patients, and a prognostic factor for prediction of tumor recurrence. Recent studies have identified other potential biomarkers for early detection of HCC, including the circulating AFP isoform AFP-L3 [11,12], des-gamma-carboxy prothrombin (DCP) [12], Golgi protein-73 (GP73) [13] and circulating miRNA [14]. The effects of other biomarkers to predict the prognosis for HCC such as vascular endothelial growth factor (VEGF), Cyclin-dependent Kinases(CDK), b-catenin/Wnt pathway and microRNAs [15] have been controversial and again none of them has been applied to the clinical settings. 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

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