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Updated: Sep 27, 2025

Preparation of Mitochondria from Ovarian Cancer Tissues and Control Ovarian Tissues for Quantitative Proteomics Analysis
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Proteomic and Transcriptomic Profiling Reveals Mitochondrial Oxidative Phosphorylation as Therapeutic Vulnerability

Caroline Xue1, Eva Corey2, Taranjit S Gujral1

  • 1Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Cancers
|April 12, 2022
PubMed

Insights

This study profiles prostate cancer patient-derived xenografts, revealing subtype-specific metabolic pathways. These findings advance understanding of aggressive prostate cancer (PC) and castration-resistant prostate cancer (CRPC) for better therapeutic options.

Area of Science:

  • Oncology
  • Genomics
  • Proteomics

Background:

  • Metastatic prostate cancer (PC) is a leading cause of cancer death with limited treatment options.
  • A lack of advanced-stage preclinical models hinders understanding of aggressive PC, including androgen receptor (AR) pathway active and AR-null castration-resistant prostate cancer (CRPC).
  • Patient-derived xenograft (PDX) models offer a valuable tool for studying human disease.

Purpose of the Study:

  • To conduct comprehensive transcriptomic and proteomic profiling of 42 LuCaP PDX prostate tumors.
  • To identify molecular markers and signaling pathways associated with AR-positive and AR-null CRPC.
  • To functionally validate key metabolic pathways in CRPC.

Main Methods:

  • Utilized 42 LuCaP PDX models for integrated transcriptomic and proteomic analysis.
  • Collected proteomic data using 71 antibodies, analyzing ~6000 data points.
  • Performed genomic analysis to identify activated pathways in different CRPC subtypes.

Main Results:

  • Identified known molecular markers for AR-positive and AR-null CRPC.
  • Genomic analysis revealed subtype-specific pathway activation: Wnt/beta-catenin, mTOR, oxidative phosphorylation in AR-positive CRPC; carbohydrate and glucose metabolism in AR-null CRPC.
  • Functionally confirmed the role of mitochondrial metabolism in AR-positive CRPC cell lines.

Conclusions:

  • Integrated transcriptomic and proteomic data from PDX models provide insights into signaling pathways in metastatic prostate cancer.
  • PDX models are crucial for dissecting the complexities of aggressive CRPC subtypes.
  • This research advances the understanding of molecular drivers in metastatic prostate cancer, potentially informing future therapies.
Keywords:
gene set expression analysismetastatic prostate cancerpatient-derived xenograftreverse phase protein arrays

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