Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.
[BACKGROUND] ONECUT2 is a lineage plasticity driver and therapeutic target in aggressive prostate cancer (PCa).
APA
Sekino Y, Li HT, et al. (2026). Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.. Biomarker research, 14(1), 18. https://doi.org/10.1186/s40364-026-00890-7
MLA
Sekino Y, et al.. "Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.." Biomarker research, vol. 14, no. 1, 2026, pp. 18.
PMID
41545903
Abstract
[BACKGROUND] ONECUT2 is a lineage plasticity driver and therapeutic target in aggressive prostate cancer (PCa). This study investigated whether ONECUT2 gene-body DNA methylation regulates its expression and assessed its potential as a biomarker in clinical specimens.
[METHODS] We analyzed associations between ONECUT2 gene-body methylation, expression, and patient survival across multiple datasets. The effect of DNA methylation on ONECUT2 expression was tested in prostate cancer cell lines using a DNA methyltransferase inhibitor (DNMTi). Validation was further performed in needle biopsy samples by targeted bisulfite sequencing for DNA methylation and RT-PCR for gene expression.
[RESULTS] ONECUT2 expression strongly correlated with gene-body DNA methylation and patient survival in multiple datasets. DNMTi treatment confirmed this relationship in prostate cancer cells. In 208 biopsies from prostate cancer patients, hypermethylation of gene-body of ONECUT2 was linked to higher ONECUT2 expression and effectively distinguished tumor from adjacent normal tissue ( < 0.001 and AUC = 0.86). It also predicted aggressive features, including higher Gleason score ( = 0.01 and AUC = 0.68), advanced T stage ( = 0.04 and AUC = 0.65), seminal vesicle invasion ( = 0.0024 and AUC = 0.76), and lymph node involvement ( = 0.0005 and AUC = 0.80).
[CONCLUSION] Assessing ONECUT2 gene-body methylation in biopsies may serve as a surrogate for ONECUT2 expression and provide predictive insights into disease progression before surgery. Furthermore, suppressing ONECUT2 through DNMTi treatment represents a potential therapeutic strategy for aggressive PCa.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s40364-026-00890-7.
[METHODS] We analyzed associations between ONECUT2 gene-body methylation, expression, and patient survival across multiple datasets. The effect of DNA methylation on ONECUT2 expression was tested in prostate cancer cell lines using a DNA methyltransferase inhibitor (DNMTi). Validation was further performed in needle biopsy samples by targeted bisulfite sequencing for DNA methylation and RT-PCR for gene expression.
[RESULTS] ONECUT2 expression strongly correlated with gene-body DNA methylation and patient survival in multiple datasets. DNMTi treatment confirmed this relationship in prostate cancer cells. In 208 biopsies from prostate cancer patients, hypermethylation of gene-body of ONECUT2 was linked to higher ONECUT2 expression and effectively distinguished tumor from adjacent normal tissue ( < 0.001 and AUC = 0.86). It also predicted aggressive features, including higher Gleason score ( = 0.01 and AUC = 0.68), advanced T stage ( = 0.04 and AUC = 0.65), seminal vesicle invasion ( = 0.0024 and AUC = 0.76), and lymph node involvement ( = 0.0005 and AUC = 0.80).
[CONCLUSION] Assessing ONECUT2 gene-body methylation in biopsies may serve as a surrogate for ONECUT2 expression and provide predictive insights into disease progression before surgery. Furthermore, suppressing ONECUT2 through DNMTi treatment represents a potential therapeutic strategy for aggressive PCa.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s40364-026-00890-7.