A Balanced Tissue Composition Reveals New Metabolic and Gene Expression Markers in Prostate Cancer

Area of Science:

• Oncology
• Metabolomics
• Bioinformatics

Background:

• Molecular analysis of patient tissues is crucial for understanding in vivo cancer variability, especially tumor metabolism.
• Heterogeneous tissue composition (epithelium, stroma, cancer) in samples can bias comparisons between cancer and normal tissues.
• Existing cell-line and animal models do not fully capture in vivo human cancer complexity.

Purpose of the Study:

• To develop and apply a strategy for removing tissue-related biases in molecular analyses of cancer patient samples.
• To investigate in vivo metabolic pathways in prostate cancer using integrated MR spectroscopy and gene expression data.
• To identify specific metabolic alterations linked to gene expression changes in prostate cancer.

Main Methods:

• Applied a sample selection strategy to balance stroma tissue content between patient groups.
• Integrated MR spectroscopy and gene expression data from the same prostate cancer tissue samples.
• Analyzed metabolic pathway changes and their correlation with gene expression profiles.

Main Results:

• Revealed in vivo metabolic pathway changes in prostate cancer previously obscured by tissue confounding.
• Identified specific metabolic alterations: lowered putrescine linked to SRM expression, reduced citrate linked to fatty acid synthesis genes, and increased succinate linked to SUCLA2 and SDHD expression.
• Highlighted significant metabolic differences between stroma, epithelium, and prostate cancer tissues.

Conclusions:

• A simple strategy effectively removes tissue-related biases in molecular analyses of patient samples.
• Accounting for heterogeneous tissue composition is essential for revealing in vivo metabolic features of cancer.
• The findings provide new insights into prostate cancer metabolism and its relationship with gene expression.