Molecular and functional landscape of malignant serous effusions for precision oncology

Nat Commun. 2024 Oct 2;15(1):8544. doi: 10.1038/s41467-024-52694-8.

Abstract

Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cohort Studies
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genomics / methods
  • Humans
  • Male
  • Middle Aged
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / pathology
  • Pleural Effusion, Malignant / genetics
  • Pleural Effusion, Malignant / metabolism
  • Pleural Effusion, Malignant / pathology
  • Precision Medicine* / methods
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Antineoplastic Agents