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

Marta Garcia de Herreros ^1,2,3,4, Natalia Jiménez ¹, Joan Padrosa ^1,2,4,5

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.
²Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain.
³Uro-Oncology Unit, Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain.
⁴Department of Medicine, University of Barcelona, 08036 Barcelona, Spain.
⁵Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain.
⁶Department of Pathology, Hospital Clínic, 08036 Barcelona, Spain.
⁷Medical Oncology Department, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, 08916 Badalona, Spain.
⁸Medical Oncology Department, Hospital del Mar, 08003 Barcelona, Spain.
⁹Medical Oncology Service, Instituto Valenciano de Oncología (IVO), 46009 Valencia, Spain.
¹⁰Medical Oncology Department, Hospital General de Granollers, 08402 Barcelona, Spain.
¹¹Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA, University of Valencia, 46010 Valencia, Spain.
¹²Medical Oncology Department, Fundació Althaia, Xarxa Assistencial Universitària de Manresa, 08242 Manresa, Spain.
¹³Department of Medical Oncology, Institut Català d'Oncologia, 17007 Girona, Spain.
¹⁴Badalona Applied Research Group in Oncology (B-ARGO), Institut Català d'Oncologia, 08916 Germans Trias i Pujol Badalona, Spain.

⁰Translational 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.

International Journal of Molecular Sciences +

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July 12, 2025

View abstract on 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.

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.

Keywords:

CHAARTED trial PTEN androgen deprivation therapy androgen receptor signaling inhibitors biomarkers docetaxel hormone-sensitive prostate cancer