Increased IFRD1 Expression in Human Colon Cancers Predicts Reduced Patient Survival

Abstract

Background: Colon cancer (CRC) is the third most common cancer worldwide. CRC develops through combinations of genetic and epigenetic changes. However, there is marked heterogeneity in the “driver gene” mutational profiles within and among colon cancers from individual patients, and these are not sufficient to explain differences in colon cancer behavior and treatment response. Global modulation of the tumor landscape may play a role in cancer behavior. Interferon-related developmental regulator 1 (IFRD1) is a transcriptional co-regulator that modulates expression of large gene cassettes and plays a role in gut epithelial proliferation following massive intestinal resection. Aims: We address the hypothesis that increased IFRD1 expression in colon cancers is associated with poorer patient survival. Methods: Tumor and normal tissue from colon cancer patient cohorts from the USA, Spain, and China were used for this study. Cancers were scored for the intensity of IFRD1 immunostaining. The primary clinical outcome was overall survival defined as time from diagnosis to death due to cancer. Kaplan–Meier method and log-rank analysis were used to assess the association between IFRD1 expression and survival. Results: Almost all (98.7%) colon cancers showed readily detectable IFRD1 expression, with immunoreactivity primarily in the tumor cytoplasm. High IFRD1 colon cancer expression was significantly associated with decreased 5-year patient survival. Patients in the American cohort with high IFRD1 expression had a poorer prognosis. Conclusions: We have demonstrated that high IFRD1 protein expression in colon cancer is associated with poorer patient prognosis, suggesting a potential role for IFRD1 in modulating tumor behavior.