Clinical Significance of Fbxw7 Tumor Suppressor Gene Mutations and Expression in Human Colorectal Cancer: A Systemic Review and Meta-analysis

Abstract

Background: Various studies investigating the clinical significance of FBXW7 mutation and/or expression have yielded inconclusive results in colorectal cancer (CRC) patients. Therefore, the present meta-analysis summarizes previous evidence and evaluates the clinical significance, including the prognostic role, of FBXW7 status in CRCs. Methods: The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Web of Science, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the relationships between FBXW7 status and clinicopathological features and survival in CRC, respectively.Results: Ten studies involving 4199 patients met the inclusion criteria and included in our meta-analysis. FBXW7 mutation/low expression was obviously correlated with advanced T stage (OR = 0.44, 95% CI: 0.27–0.74, P < 0.01) and lymph node metastasis (OR = 1.88, 95% CI: 1.40–2.53, P < 0.01), but was not associated with other parameters. Further investigation found that FBXW7 mutation/low expression predicted poor OS (HR = 1.25, 95% CI: 1.06–1.47, P < 0.01), but not DFS in CRC (HR = 1.04, 95% CI: 0.60–1.82, P = 0.88). Subgroup analysis found that FBXW7 status was obviously correlated with OS in cohorts recruited after 2009 (HR = 1.32, 95% CI: 1.17–1.50, P < 0.01), from eastern Asia (HR = 1.27, 95% CI: 1.04–1.55, P = 0.02), detected by immunohistochemistry/qRT-PCR (HR = 1.39, 95% CI: 1.22–1.59, P < 0.01), and analysed with multivariate method (HR = 1.47, 95% CI: 1.25–1.74, P < 0.01). Conclusions: This study indicates that FBXW7 status, expression level especially, is associated with OS but not DFS in CRC. FBXW7 expression level may function as a prognostic biomarker in CRC.