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Association of FOXO3 Expression with Tumor Pathogenesis, Prognosis and Clinicopathological Features in Hepatocellular Carcinoma: A Systematic Review with Meta-Analysis.

ABSTRACT: Forkhead box O3 (FOXO3), an essential transcription factor related to liver disease, has been linked to cancer progression. The most frequent primary liver tumor, hepatocellular carcinoma (HCC), has an elevated mortality rate and patient outcomes remain very poor. Here, we examined the diagnostic, prognostic and clinicopathological significance of FOXO3 expression in HCC. We systematically searched Cochrane, Embase, PubMed, Scopus and Web of Science. Articles analyzing FOXO3 levels in HCC patient samples and its relationship with tumor development, survival or clinicopathological factors were selected. Hazard ratios, odds ratios and 95% confidence intervals were extracted, estimated by Parmar method or calculated and pooled across studies. Heterogeneity was evaluated by chi-square-based Q and I² tests, while publication bias by funnel plots and Egger's test. Subgroup analysis was performed when heterogeneity was evident. The study protocol was registered in PROSPERO (CRD42021237321), and data were meta-analyzed employing STATA 16. Five studies involving 1059 HCC cases were finally included in this meta-analysis, finding that high FOXO3 levels significantly correlate with HCC development and shorter overall survival. Moreover, subgroup analysis revealed a significant association between positive FOXO3 expression and the risk of invasion. Thus, FOXO3 could function as a novel biomarker with diagnostic and prognostic value in HCC.

SUBMITTER: Fondevila F

PROVIDER: S-EPMC8582569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

Project description:BackgroundPrevious studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis.MethodsEligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models.Results21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias.ConclusionDiabetes mellitus is independently associated with both poorer overall survival and poorer disease-free survival in HCC patients.

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Association of FOXO3 Expression with Tumor Pathogenesis, Prognosis and Clinicopathological Features in Hepatocellular Carcinoma: A Systematic Review with Meta-Analysis.

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