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

Abstract

The chromatin‐organizing factor CCCTC‐binding factor (CTCF) 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 7726 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 the presence of the transmembrane protease, serine 2:ETS‐related gene 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 presurgical parameters such as clinical stage and Gleason grade of the biopsy. Comparison with key molecular alterations showed strong associations with the expression of the Ki‐67 proliferation marker and presence of phosphatase and tensin homolog deletions (P < 0.0001 each). The results of our study identify CTCF expression as a candidate biomarker for prognosis assessment in prostate cancer.

QPCT regulation by CTCF leads to sunitinib resistance in renal cell carcinoma by promoting angiogenesis

“…The elimination of CTCF confirms the multifunctional state of the protein, which is an important factor in transcriptional regulation, unique ring formation, and maintenance of chromatin structure, and is involved in protein complexes, such as adhesion proteins in interchromatin and chromatin inner rings ( 32 - 35 ). Abnormal CTCF expression has been found to induce a number of diseases or disorders, including various types of cancer ( 31 , 36 ). In particular, the downregulation of CTCF is positively associated with the dysregulation of CpG methylation patterns around genes known to be involved in tumorigenesis such as tumor protein P53 (TRp53), DNA methyltransferase 1a (DNMT4a), Runt-related transcription factor 1 (RUNX1) and CTCF] ( 37 ).…”

Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment

“…[68][69][70] . SNP rs820198 is annotated to an active CTCF (CCCTC-binding factor) binding site, and CTCF expression in linked to poor outcome in prostate cancer 71 . Although intergenic, SNP rs77112978 is near NEDD4L (MIM: 606384), whose expression is decreased in PC 72 .…”

“…RECQL5 (MIM: 603781), where SNP rs820198 is located, regulates DNA repair intermediate structures, and studies have observed elevated RECQL5 expression in other cancers such as breast (MIM: 114480) and bladder (MIM: 109800) 68–70 . SNP rs820198 is annotated to an active CTCF (CCCTC-binding factor) binding site, and CTCF expression in linked to poor outcome in prostate cancer 71 . Although intergenic, SNP rs77112978 is near NEDD4L (MIM: 606384), whose expression is decreased in PC 72 .…”

PITX1 Is a Regulator of TERT Expression in Prostate Cancer with Prognostic Power

“…The analysis of IRF1 (rabbit monoclonal antibody, Abcam, ab186384; dilution 1:450), TFAP2D [ 44 ], and CTCF [ 45 ] was performed similarly as described for PITX1. IRF-1 positive staining was usually seen in all tumor cells (100%).…”