Associations of CTCF and FOXA1 with androgen and IGF pathways in men with localized prostate cancer

To examine associations between the transcription factors CCCTC-binding factor (CTCF) and forkhead box protein A1 (FOXA1) and the androgen receptor (AR) and their association with components of the insulin-like growth factor (IGF)-pathway in a cohort of men with localized prostate cancer. Using prostate tissue samples collected during the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) trial (N = 70 to 92, depending on section availability), we assessed the abundance of CTCF, FOXA1, AR, IGFIR, p-mTOR, PTEN and IGFBP-2 proteins using a modified version of the Allred scoring system. Validation studies were performed using large, publicly available datasets (TCGA) (N = 489). We identified a strong correlation between CTCF and AR staining with benign prostate tissue. CTCF also strongly associated with the IGFIR, with PTEN and with phospho-mTOR. FOXA1 was also correlated with staining for the IGF-IR, with IGFBP-2 and with staining for activated phosphor-mTOR. The staining for the IGF-IR was strongly correlated with the AR. Our findings emphasise the close and complex links between the endocrine controls, well known to play an important role in prostate cancer, and the transcription factors implicated by the recent genetic evidence. •What is already known on this topic: CCCTC-binding factor, forkhead box protein A1 and the insulin-like growth factor axis are important in prostate cancer.•What this study adds: Novel links between endocrine controls, the IGF-axis and key transcription factors, such as FOXA1 and the AR.•How this study might affect research, practice, or policy: Optimising treatment strategies by identifyingrelevant molecular associations found in tissue from men with prostate cancer.