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Clinical and Transcriptomic Characterization of Metastatic Hormone-Sensitive Prostate Cancer Patients with Low PTEN

Marta Garcia de Herreros1,2,3,4, Natalia Jiménez1, Joan Padrosa1,2,4,5

  • 1Translational Genomics and Targeted Therapeutics in Solid Tumors Lab, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.

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|July 12, 2025
PubMed
Summary

Low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients correlates with aggressive disease and shorter survival. This PTEN-low status is linked to distinct tumor molecular profiles, suggesting new therapeutic targets.

Keywords:
CHAARTED trialPTENandrogen deprivation therapyandrogen receptor signaling inhibitorsbiomarkersdocetaxelhormone-sensitive prostate cancer

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alterations in the PTEN tumor suppressor gene are frequent in prostate cancer, often indicating aggressive disease and poor prognosis.
  • PTEN gene status may predict response to targeted therapies.

Purpose of the Study:

  • To investigate the clinical and transcriptional characteristics associated with low PTEN mRNA expression in metastatic hormone-sensitive prostate cancer (mHSPC) patients.
  • To identify potential therapeutic targets in PTEN-altered prostate tumors.

Main Methods:

  • A multicenter biomarker ambispective study involving mHSPC patients.
  • Assessment of PTEN mRNA expression using nCounter technology on tumor samples.
  • Correlation of PTEN low status with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS).
  • RNA-sequencing (RNA-Seq) for molecular characterization of PTEN low versus wild-type tumors.
  • Development of a PTEN-low related signature using CHAARTED trial microarray data.

Main Results:

  • Low PTEN mRNA expression (PTEN low) was observed in 28.2% of patients and was independently associated with significantly shorter CRPC-FS and OS.
  • PTEN low tumors exhibited overexpression of neuroendocrine, cell cycle, and DNA repair gene signatures.
  • PTEN low tumors showed reduced expression of the androgen receptor pathway and a distinct immune microenvironment.
  • A PTEN-low related signature was independently associated with CRPC-FS and OS, and identified potential therapeutic targets.

Conclusions:

  • Low PTEN mRNA expression is a significant biomarker for aggressive clinical outcomes in mHSPC patients.
  • PTEN low status is associated with a unique transcriptional profile, including altered gene expression and immune microenvironment.
  • These findings support further investigation of novel therapeutic strategies targeting PTEN alterations in prostate cancer.