Oncolipidomics: Why is lipidomic dysregulation pattern in blood similar for various cancers?

The project aims to develop advanced lipidomic techniques to create a Cancer Lipidome Atlas, enhancing early cancer detection and treatment through comprehensive lipid profiling and data integration.

Subsidie
€ 3.499.413
2023

Projectdetails

Introduction

Lipids are involved in numerous pathways of human metabolism that are related to pathological states. Alterations of lipid concentrations in the blood of cancer patients have been reported, but the biological origin is still unknown.

Importance of Lipid Dysregulation

Deciphering the mechanisms of the lipid dysregulation could dramatically change oncology because it can open new avenues for cancer detection with subsequent effective treatment and drug development targeting dysregulated pathways. Early cancer diagnosis is one of the main unmet needs in medicine, which can improve the unfavorable prognosis of patients.

Limitations of Current Lipidomics

The potential of lipidomics has not been fully explored yet because analytical workflows have limitations in terms of accurate molar quantitation and insufficient coverage of the lipidome. Biologists predict up to 100,000 lipid species in nature, but current methods typically report less than 1% of this number.

Proposed Methodology

Here, we will develop novel approaches for quantitation of more than 2,000 lipids from over 80 classes using:

  1. 13C stable isotope labeled internal standards
  2. Ultrahigh-resolution methods in liquid or supercritical fluid chromatography
  3. Mass spectrometry
  4. Ion mobility

The comprehensive characterization of the lipidome will allow us to construct a Cancer Lipidome Atlas (WP1).

Software Development

We will develop new Bayesian software for automated data processing and statistical evaluation applicable to the main lipidomic and metabolomic workflows (WP2).

Correlation with Other Omics

We will correlate lipidomics data with metabolomics, proteomics, and transcriptomics data to unravel why lipidomic dysregulation in blood has a similar pattern for various cancers (WP3).

Comparative Analysis

This strategy will be applied for the comparison of ten types of cancer with control samples in:

  • Cell lines
  • Animal models (mice and pigs)
  • Human samples (tissues and plasma)
  • Extracellular vesicles

Hypothesis

Our initial hypothesis is that the lower activity of CERS2 triggered by cancer cells can downregulate very long fatty acyl ceramides and other sphingolipids.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 3.499.413
Totale projectbegroting€ 3.499.413

Tijdlijn

Startdatum1-8-2023
Einddatum31-7-2028
Subsidiejaar2023

Partners & Locaties

Projectpartners

  • UNIVERZITA PARDUBICEpenvoerder

Land(en)

Czechia

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