Association Between Raf Kinase Inhibitor Protein Loss and Prognosis in Cancers of the Digestive System: a Meta-Analysis.

BACKGROUND:Loss of Raf kinase inhibitor protein (RKIP) may contribute to metastasis in a variety of human cancers. Many studies have evaluated whether loss of RKIP expression is a prognostic factor for survival in cancers of the digestive system, however, its predictive value remains controversial. Thus, we performed a meta-analysis to obtain a more comprehensive estimate of the prognostic value of RKIP expression in digestive system cancers.METHODS:Studies were identified by searching multiple electronic databases through December 12, 2013, and by reviewing reference lists of obtained articles. Studies reported hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between RKIP and overall survival (OS) and disease-free survival (DFS) in cancers of the digestive system were eligible, including esophageal cancer, gastric cancer, colorectal cancer and pancreatic cancer.RESULTS:Nineteen studies involving approximately 3700 participants were included in the final analysis. The pooled results suggested that loss of RKIP expression was associated with unfavorable OS (HR 0.55, 95% CI 0.46-0.65) and DFS (HR 0.46, 95% CI 0.30-0.62) among patients with digestive system cancers, whereas the difference was not statistically significant in pancreatic cancer specifically (OS, HR 0.76; 95% CI 0.51-1.01; DFS, HR 0.71; 95% CI 0.28-1.13).CONCLUSIONS:Loss of RKIP expression might be an independent indicator of poor prognosis in patients with digestive tract cancers, which includes esophageal cancer, gastric cancer and colorectal cancer. More studies are needed to further clarify the prognostic value of RKIP in pancreatic cancer. Future studies, preferably large prospective studies utilizing formal marker assessment processes, are needed to establish the prognostic value of RKIP before these results can be clinically applied.