Association of HMGB1 expression with prognosis of non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: The prognostic significance of high mobility group box 1 (HMGB1) expression in the non-small cell lung cancer (NSCLC) population remains controversial. This study endeavors to systematically evaluate the relation of HMGB1 expression levels to NSCLC prognosis via a comprehensive meta-analysis. METHODS: Embase, the Cochrane Library, Web of Science, as well as PubMed were retrieved for eligible studies until September 18, 2025. Two reviewers independently extracted relevant data and appraised the study quality. The study quality was examined via the Newcastle-Ottawa Scale (NOS). Hazard Ratio (HR) with corresponding confidence intervals (CIs) for survival outcomes were calculated and summarized respectively. Subgroup analysis, regression analysis, sensitivity analysis and publication bias were conducted to investigate the findings further. RESULTS: 11 studies on 4,527 NSCLC patients were encompassed. All eligible studies had high methodological quality. The pooled HR of OS was 1.08 (95% CI: 0.91–1.29, P = 0.356), suggesting no significant association of HMGB1 expression levels with NSCLC prognosis. Subgroup analysis of studies with sample sizes < 100 revealed a significant relation of high HMGB1 expression to poorer OS (HR: 1.51, 95% CI: 1.22–1.87). Conversely, when HMGB1 expression level was detected before chemotherapy, high HMGB1 expression was linked to improved OS (HR: 0.96, 95% CI: 0.93–0.99). CONCLUSION: This meta-analysis demonstrated that HMGB1 expression was not significantly associated with OS in the overall NSCLC population, but may have context-dependent prognostic value warranting further investigation.