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

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.