Background: Recently, several groups have reported on classifications of CRC using gene expression data to identify distinct subtypes (Guinney J, et al. Nat med 2015). Some studies found one subtype which has poor prognosis and does not respond to cet (Sadanandam A, et al. Nat Med 2013; De Sousa E Melo F, et al. Nat Med 2013). However, few subtyping studies focused on efficacy of cet as an initial therapy for mCRC. We therefore investigated whether the gene signature will predict outcomes in mCRC patients (pts) received 1st-line cet treatment. Methods: We analyzed total RNA isolated from tissue samples of 77 KRAS wild-type pts enrolled in 2 phase II trials (JACCRO CC-05:UMIN000004197 or CC-06:UMIN000007022) evaluating cet plus oxaliplatin-based chemotherapy as 1st-line treatment. Gene expression levels were measured by HTG EdgeSeq Oncology Biomarker Panel, which is comprised of probes targeting 2560 genes implicated in numbers of pathways, using next generation sequencing for quantitative analysis of targeted RNAs. Univariate Cox regression analysis was conducted for all genes that passed QC filtering. Hierarchical clustering was performed using genes under 0.005 of the Cox p-value. Results: The patient cohort comprised 57% males, median age of 63 years, 90% of performance status 0 and 15% of right colon cancer. The Cox regression analysis identified 24 genes to be with less than 0.005 of p-value for overall survival (OS). CDX2, which recently identified to be a novel prognostic marker in colon cancer (N Engl J Med 2016), ranked as first gene associated with OS as well as progression-free survival (PFS) (p= 5.56×10^-5, FDR.p= 0.058 and p= 5.09×10^-5, FDR.p= 0.053, respectively). The hierarchical clustering using the 24 genes could classify all participants into 3 groups and the Kaplan-Meier curve of the groups had a significant difference in OS (mean 13.6 vs. 19.8 vs. 28.1 months, p= 2.84e-06) but not in PFS. Conclusions: Multigene-expression signature may predict outcomes of 1st-line cet treatment in mCRC pts. These preliminary data warrants further confirmation clinical trials: validation of our findings in FIRE3 trial is ongoing.