Evaluation of A 55-Gene Classifier As A Prognostic Biomarker for Adjuvant Chemotherapy in Stage III Colon Cancer Patients

Background: Adjuvant chemotherapy reduces the recurrence risk in stage III colon cancer (CC). However, better prognostic and predictive biomarkers are required to stratify patients for treatment. We constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. Methods We retrospectively identified patients with stage III CC aged 20–79 years who received adjuvant chemotherapy with or without oxaliplatin during 2009–2012. Results Among 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity-score matching. Of these, 95 patients from each group were analyzed and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7% and 77.1%, respectively. The hazard ratios for 5-year RFS for adjuvant chemotherapy (fluoropyrimidine), with or without oxaliplatin, were 1.241 (95% CI, 0.465–3.308; P  = 0.67) and 0.791 (95% CI, 0.329–1.901; P  = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3% and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145–1.692; P  = 0.25). No RFS rate differences were noted in CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates for the MSI-like subtype in left-sided cancer were 100% and 53.9% with and without oxaliplatin, respectively. Conclusions Subclassification using 55GC and tumor sidedness revealed increased RFS of patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine with oxaliplatin relative to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies. Trial registration: The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID 000023879).