Expression of CCCTC‐binding factor (CTCF) is linked to poor prognosis in prostate cancer

Abstract

The chromatin‐organizing factor CTCF (CCCTC‐binding factor) is involved in transcriptional regulation, DNA‐loop formation and telomere maintenance. To evaluate the clinical impact of CTCF in prostate cancer we analyzed CTCF expression by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers. Normal prostate tissue showed negative to low CTCF expression, while in prostate cancers CTCF expression was seen in 7,726 of our 12,555 (61.5%) tumors and was considered low in 44.6% and high in 17% of cancers. Particularly high CTCF expression was significantly associated with presence of the TMPRSS2:ERG fusion: Only 10% of ERG negative cancers, but 30% of ERG positive cancers had high‐level CTCF expression (p < 0.0001). CTCF expression was significantly associated with advanced pathological tumor stage, high Gleason grade (p < 0.0001 each), nodal metastasis (p = 0.0122), and early biochemical recurrence (p < 0.0001). Multivariable modeling revealed that the prognostic impact of CTCF was independent from established pre‐surgical parameters such as clinical stage and Gleason grade of the biopsy. Comparison with key molecular alterations showed strong associations with expression of the Ki‐67 proliferation marker and presence of PTEN deletions (p < 0.0001 each). The results of our study identify CTCF expression as a candidate biomarker for prognosis assessment in prostate cancer.