Association between an elevated level of HMGB1 and non-small-cell lung cancer: a meta-analysis and literature review

BACKGROUND: HMGB1 has been overexpressed in the tissues or serum of patients with non-small-cell lung cancer (NSCLC) in several studies. However, the results remain inconsistent. OBJECTIVE: The aim of this study was to perform a meta-analysis to investigate the relationship between elevated level of HMGB1 and NSCLC. METHODS: Associated studies were included, and the pooled risk difference and mean difference (MD) together with 95% confidence interval (CI) were calculated. RESULTS: A total of ten relevant studies on HMGB1 expression were included in this meta-analysis. The pooled results suggested that the expression of HMGB1 in NSCLC tissues was notably higher than those in corresponding nontumor normal tissues by using immu-nohistochemistry (risk difference =0.38, 95% CI: 0.28–0.48, Z=7.67, P<0.00001, I(2)=0%), Western blot (MD =0.27, 95% CI: 0.06–0.47, Z=2.57, P<0.01), or real-time polymerase chain reaction (MD =15.15, 95% CI: 14.8–15.5, Z=2.08, P=0.04). Serum HMGB1 levels were similarly significantly higher in patients with NSCLC than those in healthy controls. The pooled MDs of HMGB1 in patients with NSCLC compared with healthy controls were 17.54 with 95% CI: 10.99–24.09, Z=5.25, P<0.00001. Two of the included studies were fully reviewed without performing meta-analysis due to the different detection methods used. The protein level of HMGB1 in patients with NSCLC of tumor, nodes, and metastasis (TNM) stages III–IV was higher than that of TNM stages I–II (P<0.047 and P<0.001, respectively). CONCLUSION: The expression levels of HMGB1 in both tissues and serum of patients with NSCLC were statistically higher than those of normal lung samples, which indicated that elevated levels of HMGB1 can reveal changes that correlated with disease progression, or even the risk of NSCLC disease progression. The elevated level of HMGB1 could also be considered as a potential biomarker for the diagnosis of patients with NSCLC.