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Cohort studyAnnals of surgical oncology · 2026

An Integrated Cell-Death Program Defines Aggressive Prostate Cancer by Coupling Ezrin to the Hippo-YAP/TAZ Axis.

Xing Luo, Zeyu Huang, Min Deng … Ji Zheng

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UrologyCohort study

High AEN score is associated with a higher rate of biochemical recurrence in prostate cancer.

An Integrated Cell-Death Program Defines Aggressive Prostate Cancer by Coupling Ezrin to the Hippo-YAP/TAZ Axis.

Xing Luo et al. · Annals of surgical oncology · 2026

Background

Prostate cancer (PCa) exhibits highly heterogeneous clinical outcomes, underscoring the need for biomarkers that more closely reflect tumor biology.

Methods

We constructed 14 PCD prognostic models in a training cohort (GSE116918, n = 248), integrated the top three (apoptosis, entosis, necroptosis) into an AEN score, and validated in two independent cohorts in PCa.

n = 248

HR = 8.02

Results

a high AEN score strongly predicts a higher risk of prostate cancer returning

n = 248

More results

High‑AEN tumors exhibited a non‑inflamed TME, predicted immunotherapy resistance, yet increased chemosensitivity.

EZR was nominated as a causal driver; knockdown of EZR suppressed proliferation, migration, and tumor growth via YAP/TAZ dysregulation.

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Conclusion

The AEN score is a robust prognostic tool linking PCD activity to PCa aggressiveness and immune evasion. EZR emerges as a functional effector and potential therapeutic target acting through Hippo signaling in PCa.

Post

An Integrated Cell-Death Program Defines Aggressive Prostate Cancer by Coupling Ezrin to the Hippo-YAP/TAZ Axis.

High AEN score is associated with a higher rate of biochemical recurrence in prostate cancer.

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