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Review
. 2021 Oct 26;13(21):5349.
doi: 10.3390/cancers13215349.

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

Flavia Fondevila  1   2 , Paula Fernández-Palanca  1   2 , Carolina Méndez-Blanco  1   2 , Tania Payo-Serafín  1   2 , Elisa Lozano  2   3 , Jose J G Marin  2   3 , Javier González-Gallego  1   2 , José L Mauriz  1   2
Affiliations
Review

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

Flavia Fondevila et al. Cancers (Basel). .

Erratum in

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.

Keywords: clinicopathological features; diagnosis; forkhead box O3; hepatocellular carcinoma; prognosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study selection. FOXO3, forkhead box O3; HCC, hepatocellular carcinoma; WOS, Web of Science.
Figure 2
Figure 2
Forest plots of the studies assessing the relationship between forkhead box O3 (FOXO3) overexpression and (a) tumor pathogenesis or (b) overall survival (OS) in hepatocellular carcinoma (HCC) patients. CI, confidence interval; HR, hazard ratio; OS, overall survival; REML, Restricted Maximum Likelihood.
Figure 3
Figure 3
Forest plots of the studies assessing the relationship between FOXO3 overexpression and specific clinicopathological features in HCC patients. AFP, alpha-fetoprotein; CI, confidence interval; HBV, hepatitis B virus; REML, Restricted Maximum Likelihood; TNM, tumor-node-metastasis.
Figure 4
Figure 4
Forest plots after subgroup analysis of the studies assessing the relationship between FOXO3 overexpression and (a) OS or (b) invasion in HCC patients. CI, confidence interval; HR, hazard ratio; NOS, Newcastle–Ottawa scale; OS, overall survival; REML, Restricted Maximum Likelihood.
Figure 5
Figure 5
Publication bias evaluation of the potential correlation of FOXO3 overexpression with (a) tumor pathogenesis, (b) OS and (c) the assessed clinicopathological features by funnel plots asymmetry. AFP, alpha-fetoprotein; CI, confidence interval; HBV, hepatitis B virus; HR, hazard ratio; IV, Inverse Variance; OS, overall survival; REML, Restricted Maximum Likelihood; TNM, tumor-node-metastasis.
See this image and copyright information in PMC

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