Molecular and functional landscape of malignant serous effusions for precision oncology
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.
Authors
- Rebekka Wegmann (ORCID: https://orcid.org/0000-0001-9616-3303)
- Fabian Arnold (ORCID: https://orcid.org/0000-0002-0556-2307)
- Aaron Fehr
- Lorenz Bankel (ORCID: https://orcid.org/0000-0002-4650-7830)
- Konstantin J. Dedes (ORCID: https://orcid.org/0000-0002-8741-9319)
- Sohyon Lee (ORCID: https://orcid.org/0000-0003-4790-4990)
- Yasmin Festl
- Berend Snijder (ORCID: https://orcid.org/0000-0003-3386-6583)
- Valentina Cappelletti (ORCID: https://orcid.org/0000-0001-6147-6545)
- Martin Zoche (ORCID: https://orcid.org/0000-0002-0421-7229)
- Christian Britschgi (ORCID: https://orcid.org/0000-0001-8831-1564)
- Peter K. Bode (ORCID: https://orcid.org/0000-0002-9633-4042)
- Holger Moch (ORCID: https://orcid.org/0000-0002-7986-2839)
- Paola Picotti (ORCID: https://orcid.org/0000-0002-4109-3552)
- Daniel Franzen (ORCID: https://orcid.org/0000-0001-6080-9555)
- Daniela Lenggenhager (ORCID: https://orcid.org/0000-0002-5382-9854)
- Kate Lau
Institutions
- SIB Swiss Institute of Bioinformatics (CH)
- University of Zurich (CH)
- ETH Zurich (CH)
- Kantonsspital Winterthur (CH)
- University Hospital of Zurich (CH)
- Immunologie-Zentrum Zürich (CH)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1038/s41467-024-52694-8
- Citations
- 9
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 2.57
Funders
- National Science Foundation
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eidgenössische Technische Hochschule Zürich