"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction".

Autor: Papaccio F; Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Via S. Allende, 84081, Baronissi, Italy. fpapaccio@unisa.it.; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain. fpapaccio@unisa.it., García-Mico B; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Gimeno-Valiente F; University College London Cancer Institute, Cancer Evolution and Genome Instability Laboratory, London, UK., Cabeza-Segura M; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Gambardella V; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain., Gutiérrez-Bravo MF; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Health Sciences Faculty, Universidad Internacional SEK (UISEK), Quito, 170120, Ecuador., Alfaro-Cervelló C; Department of Pathology, Hospital Clínico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Martinez-Ciarpaglini C; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain.; Department of Pathology, Hospital Clínico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Rentero-Garrido P; Precision Medicine Unit, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Zúñiga-Trejos S; Bioinformatic and Biostatistic Unit, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Carbonell-Asins JA; Bioinformatic and Biostatistic Unit, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Fleitas T; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain., Roselló S; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain., Huerta M; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Sánchez Del Pino MM; University Institute of Biotechnology and Biomedicine (BIOTECMED), University of Valencia, 46100, Burjassot, Spain.; Department of Biochemistry and Molecular Biology, Universitat de València, 46100, Burjassot, Spain., Sabater L; Liver, Biliary and Pancreatic Unit, Department of Surgery, Hospital Clínico Universitario of Valencia, University of Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain., Roda D; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain., Tarazona N; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain., Cervantes A; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain. andres.cervantes@uv.es.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain. andres.cervantes@uv.es., Castillo J; Department of Medical Oncology, Hospital Clínico Universitario de Valencia, INCLIVA Biomedical Research Institute, University of Valencia, Avda. Blasco Ibañez 17, 46010, Valencia, Spain. pepa.castillo@uv.es.; Centro de Investigación Biomédica en Red (CIBERONC), Instituto de Salud Carlos III, 28029, Madrid, Spain. pepa.castillo@uv.es.; Department of Biochemistry and Molecular Biology, Universitat de València, 46100, Burjassot, Spain. pepa.castillo@uv.es.
Jazyk: angličtina
Zdroj: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2023 Jan 06; Vol. 42 (1), pp. 8. Date of Electronic Publication: 2023 Jan 06.
DOI: 10.1186/s13046-022-02591-z
Abstrakt: Background: Patient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics.
Methods: We generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization. We performed drug sensitivity assays with a panel of both standard and non-standard agents in five long-term cultures, and integrated drug response with a baseline proteomic and transcriptomic characterization by SWATH-MS and RNA-seq analysis, respectively.
Results: PDOs were successfully generated from heavily pre-treated patients, including a paired model of advanced MSI high CRC deriving from pre- and post-chemotherapy liver metastasis. Our PDOs faithfully reproduced genomic and phenotypic features of original tissue. Drug panel testing identified differential response among PDOs, particularly to oxaliplatin and palbociclib. Proteotranscriptomic analyses revealed that oxaliplatin non-responder PDOs present enrichment of the t-RNA aminoacylation process and showed a shift towards oxidative phosphorylation pathway dependence, while an exceptional response to palbociclib was detected in a PDO with activation of MYC and enrichment of chaperonin T-complex protein Ring Complex (TRiC), involved in proteome integrity. Proteotranscriptomic data fusion confirmed these results within a highly integrated network of functional processes involved in differential response to drugs.
Conclusions: Our strategy of integrating PDOs drug sensitivity with SWATH-mass spectrometry and RNA-seq allowed us to identify different baseline proteins and gene expression profiles with the potential to predict treatment response/resistance and to help in the development of effective and personalized cancer therapeutics.
(© 2023. The Author(s).)
Databáze: MEDLINE
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