Clinicopathological significance and prognostic role of p-STAT3 in patients with hepatocellular carcinoma

Abstract

Background and aim: Constitutive activation of STAT3 through its phosphorylation (p-STAT3) plays a key role in the development and progression of various cancers. However, the relationship between p-STAT3 expression and the clinicopathological features and prognostic value in patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to evaluate the role of p-STAT3 in HCC.

Methods: The PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese Wanfang databases were searched using the appropriate terms to find the relevant studies on p-STAT3 and HCC. The relationship between p-STAT3 expression and clinicopathological characteristics and prognostic value was established. Pool odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using the STATA 14.2 software.

Results: The eight articles included in this meta-analysis comprised 752 patients. Expression of p-STAT3 was associated with incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage of HCC, but it was not related to gender, alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), number of tumors, and tumor differentiation. Additionally, the expression of p-STAT3 was related to a poor 3- and 5-year overall survival rate and disease-free survival rate.

Conclusion: Expression of p-STAT3 was associated with the incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage. Thus, p-STAT3 can be a reliable prognostic biomarker for HCC. Further high-quality studies with larger numbers of patients are needed.

Keywords: hepatocellular carcinoma; meta-analysis; p-STAT3; prognosis.

Figure 1

Flow diagram depicting the study selection.

Figure 2

Forest plot of studies evaluating the association between p-STAT3 expression and clinicopathogical features including expression (A), gender (B), age (C), HBsAg (D), liver cirrhosis (E), AFP (F), tumor size (G), number of tumors (H), vascular invasion (I), tumor differentiation (J), and TNM stage (K). Note: Weights are from random-effects analysis. Abbreviations: AFP, alpha-fetoprotein; HBsAg, hepatitis B surface antigen; OR, odds ratio.

Figure 3

Pooled analysis for the association between p-STAT3 expression and the 3-year OS rate (A: Forest plot, D: Begg’s publication bias plot), the 5-year OS rate (B: Forest plot, E: Begg’s publication bias plot), and the DFS rate (C: Forest plot, F: Begg’s publication bias plot). Abbreviations: DFS, disease-free survival; HR, hazard ratio; OS, overall survival.

Figure 4

Begg’s publication bias plot for the p-STAT3-related studies including expression (A), gender (B), age (C), HBsAg (D), liver cirrhosis (E), AFP (F), tumor size (G), number of tumors (H), vascular invasion (I), differentiation (J), and TNM stage (K). Abbreviations: AFP, alpha-fetoprotein; HBsAg, hepatitis B surface antigen; OR, odds ratio.

Figure 4

Begg’s publication bias plot for the p-STAT3-related studies including expression (A), gender (B), age (C), HBsAg (D), liver cirrhosis (E), AFP (F), tumor size (G), number of tumors (H), vascular invasion (I), differentiation (J), and TNM stage (K). Abbreviations: AFP, alpha-fetoprotein; HBsAg, hepatitis B surface antigen; OR, odds ratio.