Alteration of FBXW7 is Associated with Worse Survival in Patients Undergoing Resection of Colorectal Liver Metastases

Background For patients undergoing resection of colorectal liver metastases (CLMs), the prognostic role of somatic gene alterations is increasingly recognized. F-box/WD repeat-containing protein 7 (FBXW7) is a tumor suppressor gene found in approximately 10% of patients with colorectal cancer. The aim of this study is to assess the association of FBXW7 with overall survival after CLM resection. Methods Patients who underwent initial CLM resection during 2001-2016 and had genetic sequencing data were studied. Risk factors for overall survival (OS) were evaluated with Cox proportional hazards models using backward elimination. Results Of 2045 patients who underwent CLM resection during the study period, 476 were included. The majority (90.5%) underwent prehepatectomy chemotherapy. A total of 27 patients (5.7%) had FBXW7 alteration, along with 240 (50.4%) RAS, 337 (70.8%) TP53, 51 (10.7%) SMAD4, and 27 (5.7%) BRAF. Cox proportional hazards model analyses including 5 somatic gene alteration status and 12 clinicopathologic factors revealed FBXW7(hazard ratio [HR] 1.99, P = 0.015), BRAF (HR 2.47, P = 0.023), RAS (HR 2.42, P < 0.001), TP53 (HR 2.00, P < 0.001), and SMAD4 alterations (HR 1.90, P = 0.004) as significantly associated with OS, together with three clinicopathologic factors, prehepatectomy chemotherapy > 6 cycles (HR 1.51, P = 0.021), number of CLM (HR 1.05, P = 0.007), and largest liver metastasis diameter (HR 1.07, P = 0.023). The covariate-adjusted 5-year OS was significantly lower in patients with FBXW7 alteration than in patients with FBXW7 wild-type (40.4% vs.59.4%, P = 0.015). Conclusions FBXW7 alterations are associated with worse survival after CLM resection. The information on multiple somatic gene alterations is imperative for risk stratification and patient selection for CLM resection.

Automated summary

The study showed that FBXW7 alterations are associated with worse survival after colorectal liver metastases (CLMs) resection. In addition to FBXW7, other somatic gene alterations and clinicopathologic factors were also significantly associated with overall survival, emphasizing the importance of assessing multiple genetic markers for risk stratification and patient selection in CLM resection.