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Chromatin regulators and stratify prostate cancer risk and reveal -driven progression via PI3K/AKT pathway.

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Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 📖 저널 OA 100% 2022: 3/3 OA 2024: 7/7 OA 2025: 29/29 OA 2026: 5/5 OA 2022~2026 2026 Vol.38(1) p. 83-99 OA
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출처

Wang Z, Wang J, Chen S, Wu R, Tuo Z, Ye L

📝 환자 설명용 한 줄

[OBJECTIVE] To identify chromatin regulators (CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence (BCR) after radical prostatectomy (RAP) in prostate cancer

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  • p-value P=0.003
  • p-value P=0.010
  • 95% CI 1.05-4.02
  • HR 2.05

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APA Wang Z, Wang J, et al. (2026). Chromatin regulators and stratify prostate cancer risk and reveal -driven progression via PI3K/AKT pathway.. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 38(1), 83-99. https://doi.org/10.21147/j.issn.1000-9604.2026.01.06
MLA Wang Z, et al.. "Chromatin regulators and stratify prostate cancer risk and reveal -driven progression via PI3K/AKT pathway.." Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, vol. 38, no. 1, 2026, pp. 83-99.
PMID 41852923 ↗

Abstract

[OBJECTIVE] To identify chromatin regulators (CRs)-based molecular subtypes and risk scores for accurately predicting biochemical recurrence (BCR) after radical prostatectomy (RAP) in prostate cancer (PCa) patients.

[METHODS] Differentially expressed genes (DEGs) between tumor and normal samples from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases were intersected with CR-related and prognostic genes. Consensus clustering, risk score analysis, functional analysis, immune microenvironment, m6A, and heterogeneity assessments were performed using R software. validation used DU145 and C42B PCa cell lines. Topoisomerase II alpha () was knocked down via siRNA. Assays included CCK-8 proliferation, colony formation, transwell migration/invasion, wound healing, and western blotting (WB) for pathway validation.

[RESULTS] and peroxisome proliferator-activated receptor gamma coactivator 1-alpha () defined molecular subtypes and a risk score in TCGA, validated in a GEO dataset. Cluster 2 exhibited significantly shorter BCR-free survival . cluster 1 in TCGA [hazard ratio (HR): 2.21; 95% confidence interval (95% CI): 1.32-3.73; P=0.003)], GEO (HR: 2.05; 95% CI: 1.05-4.02; P=0.010), and MSKCC2010 (HR: 5.93; 95% CI: 1.96-17.87; P<0.001). Similar survival differences were observed between high- and low-risk groups (defined by the median risk score). Cluster 2 showed greater tumor heterogeneity and higher m6A gene expression. Gene set variation analysis (GSVA) revealed downregulated cell-cycle pathways in cluster 2, alongside suppressed tumor-infiltrating immune cells. knockdown significantly impaired PCa cell proliferation, colony formation, migration, and invasion. Mechanistically, it suppressed phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway activation, reducing phosphorylated PI3K and AKT levels without altering total protein.

[CONCLUSIONS] and effectively stratify PCa subtypes for RAP patients. TOP2A drives malignant progression via the PI3K/AKT pathway.

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