Clinicopathological significance of Gli1 expression in hepatocellular carcinoma: a meta-analysis

This meta-analysis assessed the clinicopathological significance of GLI1 in hepatocellular carcinoma (HCC). We systematically searched PubMed, Web of Science, Embase, Cochrane Library, Wan Fang, and CNKI for studies through October 2025. Studies assessing GLI1 by immunohistochemistry in HCC tissue and reporting its clinicopathological correlations were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Publication bias and sensitivity analyses were performed, and subgroup analyses were conducted when > 4 studies were available. Analysis of ten studies (n = 974) showed significant GLI1 upregulation in HCC versus non-tumorous tissues (OR = 7.06, 95% CI 3.21-15.54, P < 0.0001). Elevated GLI1 was associated with intrahepatic metastasis (OR = 2.51, 95% CI 1.42-4.43, P = 0.002), vascular invasion (OR = 2.98, 95% CI 1.64-5.42, P < 0.001), hepatitis B virus (HBV) infection (OR = 2.32, 95% CI 1.28-4.20, P = 0.006). The significance of advanced pTNM stage (OR = 3.03, 95% CI 1.29-7.10, P = 0.011) disappeared after adjusting for publication bias (adjusted OR = 1.94, 95% CI 0.85-4.40). No significant associations were found with patient age, liver cirrhosis, serum AFP level, and tumor size. Findings are based on observational studies with heterogeneity in GLI1 assessment; evidence certainty for several outcomes is low or very low. These findings support the hypothesis that GLI1 might be involved in aggressive HCC phenotypes and warrant its investigation in future, standardized prospective studies to assess its potential clinical utility.Trial registration: The study protocol was registered in the International Prospective Register of Systematic Reviews (CRD42024500731).