High Expression of CUL9 Is Prognostic and Predictive for Adjuvant Chemotherapy in High-Risk Stage II and Stage III Colon Cancer

SIMPLE SUMMARY: This retrospective study evaluated the clinical implications of CUL9 expression on the prognosis and the predictive value for postoperative adjuvant chemotherapy in consecutive patients with colon cancer. Among all 1078 patients, high expression of CUL9 was an independent prognostic factor on disease-free survival and overall survival. Prognostic biomarkers are keys to the risk stratification of patients and the decision to recommend adjuvant chemotherapy. Among 564 patients with high-risk stage II and stage III disease who were recommended to receive the standard 6 months of chemotherapy, those with high CUL9 expression from the full dose group had better disease-free survival than those from the reduced dose group. A test for the interaction between CUL9 expression and the treatment reached significance and was not confounded by T stage, N stage and histopathological grade. This indicated that CUL9 expression may further filter those patients to identify truly high-risk cases that benefit from the full dose of the standard 6 months of chemotherapy. ABSTRACT: We evaluated the clinical implications of CUL9 expression on the prognosis and the predictive value for adjuvant chemotherapy in colon cancer. A total of 1078 consecutive patients treated with radical resection from 2008 to 2012 were included. Formalin-fixed, paraffin-embedded specimens were used as immunohistochemistry (IHC) for CUL9. For all patients, high expression of CUL9 was identified as an independent prognostic factor for overall survival (HR = 1.613, 95% CI 1.305–1.993, p < 0.001) and disease-free survival (HR = 1.570, 95% CI 1.159–2.128, p = 0.004). The prognostic value of high CUL9 expression was confirmed in an independent validation cohort from the GEO database. The efficacy of adjuvant chemotherapy was analyzed among patients with high-risk stage II and stage III disease. Those with high CUL9 expression from the full dose group had better disease-free survival (HR = 0.477, 95% CI 0.276–0.825, p = 0.006) than those from the reduced dose group. The interaction test between CUL9 expression and the treatment reached significance and was not confounded by T stage, N stage and histopathological grade. In general, high expression of CUL9 was an independent prognostic factor in patients with colon cancer. In those with high-risk stage II and stage III disease, high expression of CUL9 was associated with the benefit from standard 6-months adjuvant chemotherapy regimens.