The Association of HMGB1 Expression with Clinicopathological Significance and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis and Literature Review

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.

Relationship between TRAF6 and deterioration of HCC: an immunohistochemical and in vitro study

“…HCC is one of the most common, aggressive and lethal cancers in the world [ 26 ]. Owing to its burden to human health, early and effective diagnosis is of vital importance.…”

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

“…These cancer hallmarks include: sustainment of proliferative signaling; evasion of growth suppressors; avoidance of immune destruction; enablement of replicative immortality; tumor-promoting inflammation; activation of invasion and metastasis; induction of angiogenesis; genome instability and mutation; resistance to cell death; and deregulation of cellular energetics [34]. Meanwhile, higher HMGB1 expression was detected in late stage patients with hepatocellular carcinoma [35] and squamous-cell carcinoma of the head and neck [26]. In this respect, HMGB1 can be considered as an oncoprotein.…”

The role of high‐mobility group protein box 1 in lung cancer

“…Previous studies showed that the increased expression of HMGB1 in many malignant tumors has been associated with progressive tumor proliferation, invasion, metastasis, and poor prognosis, for example, hepatocellular carcinoma, osteosarcoma, bladder cancer, gastric cancer, colon cancer, breast cancer, and mesothelioma. [70][71][72][73][74][75][76][77][78][79][80] Besides, the overexpression of HMGB1 was closely related to the level of tumor invasion and the stage of lymph node metastasis in colon and colorectal cancer. 81 Of note, the overexpression of HMGB1, TLR4, and MyD88 are correlated with tumor-node-metastasis stage and lymph node metastasis in gastric cancer, which proves poor prognosis.…”