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  1. Home
  2. Prognostic Expression Signature Of Rb1, Pten, And Tp53 Genes In Patients With Metastatic Hormone-sensitive Prostate Cancer Treated With Androgen Receptor Pathway Inhibitors.
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  2. Prognostic Expression Signature Of Rb1, Pten, And Tp53 Genes In Patients With Metastatic Hormone-sensitive Prostate Cancer Treated With Androgen Receptor Pathway Inhibitors.

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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
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Prognostic Expression Signature of RB1, PTEN, and TP53 Genes in Patients with Metastatic Hormone-sensitive Prostate

Marta Garcia de Herreros1,2,3, Natalia Jiménez1, Leonardo Rodríguez-Carunchio3,4

  • 1Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

European Urology Open Science
|November 6, 2024

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
Aggressive-variant prostate cancerAndrogen deprivation therapyAndrogen receptor pathway inhibitorsBiomarkersHormone-sensitive prostate cancerTumor suppressor genes

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A low tumor suppressor gene (TSG) expression signature indicates poor outcomes in metastatic hormone-sensitive prostate cancer patients treated with androgen deprivation therapy and androgen receptor pathway inhibitors. This signature is linked to aggressive disease and visceral metastases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alterations in tumor suppressor genes (TSGs) like RB1, PTEN, and TP53 are linked to aggressive prostate cancer and treatment resistance.
  • A previously validated TSG-low signature predicted poor outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) patients receiving androgen deprivation therapy (ADT) ± docetaxel.

Purpose of the Study:

  • To validate the TSG-low signature in mHSPC patients treated with ADT plus an androgen receptor pathway inhibitor (ARPI).
  • To explore clinical characteristics at progression based on TSG expression status.

Main Methods:

  • Retrospective multicenter study analyzing TSG mRNA expression via nCounter in formalin-fixed, paraffin-embedded samples.
  • Kaplan-Meier and multivariate Cox analyses correlated TSG expression with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS).

Main Results:

  • The TSG-low signature (16.8% of patients) was associated with visceral metastases (p=0.013), high-risk disease (p=0.038), and higher Gleason scores (p=0.026).
  • TSG-low status correlated with shorter CRPC-FS (HR 1.9; p=0.046) and increased aggressive variants of prostate cancer (AVPC) frequency (p=0.01).

Conclusions:

  • The TSG-low signature is a confirmed adverse prognostic factor in mHSPC patients treated with ADT + ARPI.
  • This signature is associated with the development of aggressive variants of prostate cancer.
  • Prospective validation is required to guide specific therapeutic strategies for patients with TSG-low prostate cancer.