Association between SOCS3 hypermethylation and HBV-related hepatocellular carcinoma and effect of sex and age

Abstract

Background: Suppressor 3 of cytokine signaling (SOCS3) hypermethylation has been reported to participate in hepatocellular carcinoma (HCC) development and progression, but conflicting results were published. This study aimed to analyze the clinical effects of SOCS3 hypermethylation in HCC and the effects of sex and age on SOCS3 hypermethylation in HCC.Methods: Databases were searched for relevant case-control and cohort studies on SOCS3 hypermethylation in HBV-related HCC. In vitro and in vivo studies and studies of patients with serious comorbidities were excluded. Review Manager 5.2 was used to estimate the effects of the results among the selected studies. Forest plots, sensitivity analysis, and bias analysis for the included studies were also conducted.Results: Finally, 8 relevant studies met the inclusion criteria. A significant difference in SOCS3 hypermethylation in HCC was found between tumor and nontumor groups (the odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.48-2.73, P < .00001; P for heterogeneity = .39, I 2 = 5%). The meta-analysis suggested no significant difference in the effect of sex (OR = 1.00, 95% CI: 0.76-1.31, P = .76; P for heterogeneity = .44, I 2 = 0%) and age on SOCS3 hypermethylation in HCC (OR = 1.11, 100% CI: 0.78-1.29, P = .03; P for heterogeneity = .14, I 2 = 36%). Limited publication bias was observed in this study.Conclusion: SOCS3 hypermethylation is associated with HBV-related HCC. Sex and age do not affect the association between SOCS3 hypermethylation and HCC. SOCS3 might be a treatment target for HCC.Abbreviations: CIs = confidence intervals, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, NOS = Newcastle-Ottawa Scale, OR = odds ratio, SOCS = suppressors of cytokine signaling, SOCS3 = suppressor 3 of cytokine signaling.

Effects of DNA methylation and its application in inflammatory bowel disease (Review)

“…The physiological processes by which long-term inflammatory reactions in the colon may encourage CRC remain unclear; they may involve the decreased negative control of IL-6 signaling toward STAT3 activations through the loss of SOCS3 expression, releasing the full toxic potential of this transcription factor ( 61 ). It has also been discovered that hepatocellular carcinoma (HCC) linked to the hepatitis B virus is associated with SOCS3 hypermethylation ( 91 ).…”

Recent Advances in the Knowledge of the Mechanisms of Leptin Physiology and Actions in Neurological and Metabolic Pathologies

“…The leptin signaling cascade can be involved in changes in susceptibility to cancer processes and it has been suggested that genetic variations in JAK2 are involved in the generation of several signs of myeloproliferative neoplasms [ 227 ], as well as SOCS3 polymorphisms, that may favor the progression towards liver fibrosis and hepatocellular carcinoma [ 228 ]. Hypermethylation of SOCS3 has been reported to contribute to hepatocellular carcinoma development and progression [ 229 ].…”

Dysregulation of Liver Regeneration by Hepatitis B Virus Infection: Impact on Development of Hepatocellular Carcinoma

“…It is proposed that the reduced expression of SOCS3 results in sustained activation of the IL-6/STAT3 pathway, which could be essential to hepatocarcinogenesis [ 91 ]. Similarly, a recent meta-analysis work demonstrated that the SOCS3 hypermethylation is associated with HBV-related HCC [ 92 ], and this may validate the possibility of SOCS3 expression or methylation status of the SOCS3 gene as a prognosis marker for HCC associated with HBV infection [ 93 ].…”