Establishing and Characterizing the Molecular Profiles, Cellular Features, and Clinical Utility of a Patient-Derived...

Area of Science:

• Urology
• Oncology
• Translational Research

Background:

• Benign prostatic hyperplasia (BPH) significantly impacts quality of life due to lower urinary tract symptoms.
• Effective preclinical models are essential for understanding BPH pathophysiology and developing novel treatments.

Purpose of the Study:

• To establish and characterize a patient-derived xenograft (PDX) model for benign prostatic hyperplasia (BPH).
• To investigate the molecular and cellular mechanisms underlying BPH using this novel model.
• To evaluate the therapeutic response of the BPH PDX model to finasteride.

Main Methods:

• Human BPH and normal prostate tissues were implanted into immunodeficient mice to create PDXs.
• Histology, immunohistochemistry, ELISA, transcriptomics, and proteomics were used to analyze PDX characteristics.
• PDXs were assessed for weight, proliferation, apoptosis, and molecular profiles over time.
• Response to finasteride treatment was evaluated in the BPH PDX model.

Main Results:

• PDXs successfully recapitulated the histologic and molecular features of the original human prostate tissues.
• BPH PDXs exhibited increased weight and cellular proliferation compared to normal PDXs.
• Molecular profiling identified specific BPH-related gene and protein expression patterns, including BMP5 and CXCL13.
• Finasteride treatment demonstrated efficacy in the BPH PDX model, reducing proliferation and increasing apoptosis.

Conclusions:

• The developed BPH PDX model accurately reflects human disease characteristics.
• This model provides a valuable platform for preclinical evaluation of BPH therapeutics.
• The BPH PDX model facilitates research into BPH microenvironment interactions and potential therapeutic targets.