The Prognostic Value Of KRAS In Patients With Colorectal Cancer With Unresectable Liver Metastases

?Objective?To assessed the characteristics and prognostic roles of KRAS mutations in patients with colorectal cancer with liver metastasis(CRLM)with unresectable liver metastases.?Method?Data on KRAS mutations in 93 patients with CRLM who only underwent primary resection at our institution between 2010 and 2018 were analyzed.?~2 test or Fisher exact test were used to analyze the relationship between KRAS gene mutation and clinicopathological factors.Kaplan-Meier and Cox proportional hazard models were used to evaluate the prognostic significance of KRAS mutations.?Result?KRAS mutations were identified in 41.9%of patients(39/93).The mutations was mainly concentrated in codon 12 and 13 and were primarily single-point mutations.Among 39 cases,G12D(9/39),G12V(8/39),and G13D(8/39)mutations were dominant.There were no significant differences in features between wild-type and mutant KRAS(P>0.05).Patients with mutant KRAS had significantly shorter median overall survival(OS)and progression-free survival(PFS)than those with wild-type KRAS(P<0.05).Moreover,patients with codon 12 mutations had worse OS(HR=2.527;95%CI,1.349–4.734;P=0.004)and PFS(HR=1.830;95%CI,1.041–3.216;P=0.036)than those with wild-type KRAS,whereas codon 13 mutations were not associated with prognosis(P>0.05).Among the five most common mutations in codons 12,only G12V(HR=3.400;95%CI:0.1.432-8.073;P=0.006)and G12D(HR=2.568;95%CI:1.087-6.070;P=0.032)were associated with worse OS.Additionally,among patients who showed disease progression,only G12C mutation was associated with worse PFS than patients with wild-type KRAS(HR=8.676;95%CI:3.274-22.99;P<0.001).?Conclusion?KRAS codon 12 mutations were independent prognostic factors in patients with CRLM with unresectable liver metastases.G12D and G12V mutations were associated with worse OS,whereas G12C mutation was associated with decreased PFS.