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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
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Increasing Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival.

Xiaozhuo Liu1, Eduardo Cortes2,3, Yibing Ji1

  • 1Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

Biorxiv : the Preprint Server for Biology
|June 3, 2025
PubMed
Summary

Cancer stemness, a measure of cell-like traits, increases with prostate cancer (PCa) progression. Higher stemness predicts poor outcomes and can be quantified using a new PCa-Stem Signature.

Keywords:
AR signalingProstate canceraggressivenessheterogeneityplasticitystemness

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Area of Science:

  • Oncology
  • Genomics
  • Molecular Biology

Background:

  • Cancer progression is linked to loss of cell differentiation and gain of stem cell properties, termed "stemness".
  • Quantifying stemness could offer insights into prostate cancer (PCa) development and clinical outcomes.

Purpose of the Study:

  • To assess if transcriptome-derived Stemness scores can quantitatively track PCa progression, therapy resistance, metastasis, plasticity, and patient survival.
  • To investigate the relationship between Stemness, androgen receptor activity (AR-A), and key genetic alterations in PCa.

Main Methods:

  • Integrative analysis of transcriptomic data from 87,183 PCa samples across 26 datasets.
  • Calculation of a general Stemness score and development of a 12-gene "PCa-Stem Signature".

Main Results:

  • A progressive increase in Stemness and decline in AR-A were observed along the PCa continuum, with metastatic castration-resistant PCa (mCRPC) showing the highest Stemness.
  • Both Stemness scores and the PCa-Stem Signature correlated with and predicted poor clinical outcomes.
  • Mechanistic insights suggest AR-A promotes early-stage Stemness, while MYC amplification and RB1 loss drive high Stemness in mCRPC.

Conclusions:

  • Stemness serves as a robust quantitative measure of PCa aggressiveness.
  • The findings provide a scalable framework for PCa risk stratification and clinical management.