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Multi-omics integration reveals CYTL1 and H6PD as key regulators of tumor metabolism in mesothelioma

Jiao Ma1, Huilin Zhang2, Luanxue Yu3

  • 1Department of Pathology, Zhejiang Hospital, Hangzhou, Zhejiang Province, China.

Genes & Genomics
|August 25, 2025
PubMed
Abstract

Insights

This study identifies CYTL1 and H6PD as key regulators of mesothelioma tumor metabolism. CYTL1 shows promise as a therapeutic target for this aggressive cancer, while H6PD also warrants further investigation.

Area of Science:

  • Oncology
  • Genomics
  • Metabolomics

Background:

  • Mesothelioma is a rare, aggressive cancer with limited treatment options and poor prognosis.
  • Identifying effective biomarkers and therapeutic targets remains a significant challenge in mesothelioma research.

Purpose of the Study:

  • To employ a multi-omics approach to discover novel biomarkers and therapeutic targets for mesothelioma.
  • To elucidate the molecular mechanisms underlying mesothelioma progression and drug response.

Main Methods:

  • Integrated a multi-omics framework including druggable genomics, Mendelian randomization (MR), and single-cell RNA sequencing (scRNA-seq).
  • Utilized MR analysis for target prediction, cross-referenced with mesothelioma-specific single-cell markers, and validated findings using summary data-based MR and protein quantitative trait loci analysis.
  • Performed functional enrichment analyses (Gene Ontology, KEGG, GSEA) and assessed drug sensitivity using the GDSC2 dataset, followed by molecular docking simulations.

Main Results:

  • Identified CYTL1 and H6PD as potential biomarkers and therapeutic targets in mesothelioma.
  • CYTL1 correlated with poor prognosis and reduced drug sensitivity, whereas H6PD exhibited an inverse relationship. Compounds targeting CYTL1 were identified.
  • Metabolic mediation analysis revealed CYTL1 influences mesothelioma via levulinoylcarnitine, and H6PD regulates tumor metabolism through specific metabolite ratios.

Conclusions:

  • CYTL1 and H6PD are identified as critical regulators of tumor metabolism in mesothelioma.
  • CYTL1 emerges as a promising therapeutic target for mesothelioma, meriting further clinical investigation.
  • This study highlights the power of multi-omics strategies in uncovering novel therapeutic avenues for challenging cancers like mesothelioma.
Keywords:
CYTL1H6PDMRMesotheliomaMetabolismscRNA-seq

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