Prognostic value of SMAD4 in resectable pancreatic cancer

Abstract Introduction The tumor gene SMAD4 was genetically inactivated in approximately half of pancreatic cancer (PC) patients. The correlation of SMAD4 gene expression in PC and its prognosis remains inconclusive. The aim of this study was to evaluate the association between loss of SMAD4 expression and the outcome of resectable PC. Materials and Methods A systematic review of the relevant electronic databases was conducted between SMAD4 expression and the outcome of PC patients until December 2020, including PubMed, Web of Science, and the China Journal Net. A meta-analysis was performed using STATA 12.0 and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between SMAD4 gene expression and the prognosis of PC patients. Results Twelve studies were included. Our meta-analysis illustrated that there were no significant associations between the loss of SMAD4 gene expression and overall survival in resectable PC (HR=1.38, 95% CI 0.98–1.81). In addition, there was no evidence of publication bias, as showed by Begg's and Egger's test. There was no correlation between the loss of SMAD4 expression and local recurrence (OR=0.97, 95% CI 0.52–1.80, p=0.914), while the loss of SMAD4 gene expression was associated with increased risk of distant recurrence (OR=1.36, 95% CI 1.08–1.70, p=0.008). Conclusions After PC resection, the loss of SMAD4 gene expression was correlated with higher risk of distant recurrence, but not with local recurrence nor overall survival.