Related Experiment Video
Updated: Jun 12, 2025
Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
Published on: October 2, 2014
Tumor specimen cold ischemia time impacts molecular cancer drug target discovery
Silvia von der Heyde1, Nithya Raman1, Nina Gabelia1
1Indivumed GmbH, Hamburg, Germany.
Abstract:
Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research.
Insights
Ischemia time significantly impacts tumor tissue quality, affecting mRNA, protein, and phosphosite expression. Longer ischemia times disrupt molecular profiles, particularly immune response pathways, crucial for cancer research and drug target discovery.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumor tissue collections are vital for identifying cancer pathways and therapeutic targets.
- Tissue quality, influenced by molecular changes from ischemia and decay, dictates data reliability.
- Ischemia time is a critical factor affecting biomolecule integrity in preserved tissues.
Purpose of the Study:
- To investigate the impact of ischemia time on molecular profiles (mRNA, protein, phosphosites) in tumor and adjacent normal tissues.
- To assess how ischemia affects molecular dysregulation across different solid tumor types.
- To determine the relationship between ischemia time and specific biological pathways affected.
Main Methods:
- Analysis of mRNA, protein, and phosphosite expression in 1664, 1818, and 1800 tumor/normal tissue pairs, respectively.
- Comparison of molecular profiles based on varying ischemia times across four solid tumor types (CRC, HCC, LUAD, LUSC NSCLC).
- Proteomic analysis to identify pathways dysregulated by prolonged ischemia.
Main Results:
- Ischemia exceeding 15 minutes significantly impacted molecular profiles in colorectal cancer (CRC), affecting 12.5% of mRNAs, 25% of proteins, and 50% of phosphosites.
- Hypoxia- and decay-induced molecular dysregulation intensified with longer ischemia times across all studied tumor types.
- Proteomics revealed that ischemia > 15 minutes primarily dysregulated immune response proteins, with less impact on metabolic processes.
Conclusions:
- Ischemia time is a critical determinant of tissue collection quality for cancer research.
- Adherence to strict ischemia time limits is essential for reliable molecular data in target discovery and validation.
- Understanding ischemia's impact is crucial for interpreting molecular data and developing effective cancer therapies.
More Related Videos
08:32Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
06:00Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
