Evidence map›Paper›PMID 41545903›Full record

ArticleBiomarker research2026

Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.

Yohei Sekino, Hong-Tao Li, Masatomo Kaneko, Yuta Inoue, Lorenzo Storino Ramacciotti, Rongying Lu, Zhenzhong Deng, Xinyi Zhou, Michelle Mingxue Song, Aditya Desai and 11 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Yohei Sekino *Department of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Hong-Tao Li *Department of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Masatomo KanekoDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Yuta InoueDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Lorenzo Storino RamacciottiDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Rongying LuDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Zhenzhong DengDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Xinyi ZhouDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Michelle Mingxue SongDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Aditya DesaiDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Mingda JinZymo Research Corp, Irvine, CA, USA.
Wei GuoZymo Research Corp, Irvine, CA, USA.
Xiaojing YangZymo Research Corp, Irvine, CA, USA.
Jeffrey BhasinZymo Research Corp, Irvine, CA, USA.
Nobuyuki HinataDepartment of Urology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Michael R FreemanDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Inderbir GillDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Manju AronDepartment of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Steven Yong CenDepartment of Radiology/Neurology, University of Southern California, Los Angeles, CA, 90089, USA.
Andre Luis AbreuDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA.
Gangning LiangDepartment of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, 90089, USA. gliang@usc.edu.

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Targeting DNA Methylation and the Cancer EpigenomeR35CA209859 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI PETER A JONES · 2017 to 2026
$11.9M
Grants-in-Aid for Scientific Research 19K18586NCI NIH HHS P30 CA014089NCI NIH HHS R35 CA209859
6 · The paper itself

Abstract

backgroundONECUT2 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.

methodsWe 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.

resultsONECUT2 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 (p < 0.001 and AUC = 0.86). It also predicted aggressive features, including higher Gleason score (p = 0.01 and AUC = 0.68), advanced T stage (p = 0.04 and AUC = 0.65), seminal vesicle invasion (p = 0.0024 and AUC = 0.76), and lymph node involvement (p = 0.0005 and AUC = 0.80).

conclusionAssessing 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.

Indexed as

Aggressive prostate cancerBiomarkerDNA methylationGene-bodyGene expressionNeedle biopsyONECUT2Prostate cancerTherapeutic target

Identifiers

PMID41545903
PMCPMC12829032

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