Portal de investigación
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction"
Fecha de publicación:
Fecha Ahead of Print:
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Sanchez Del Pino, Manuel M
Grupos y Plataformas de I+D+i
Abstract
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).
Datos de la publicación
- ISSN/ISSNe:
- 0392-9078, 1756-9966
- Tipo:
- Article
- Páginas:
- 8-8
- PubMed:
- 36604765
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH BioMed Central
Citas Recibidas en Web of Science: 48
Documentos
Filiaciones
Keywords
- Colorectal cancer; Organoids; Quantitative proteomics; Precision medicine; Drug resistance; Transcriptomics; Proteotranscriptomics integrative functional network analysis
Financiación
Proyectos y Estudios Clínicos
CONTRATOS JUAN RODES
Investigador Principal: DESAMPARADOS RODA PEREZ
2016/197 . INSTITUTO SALUD CARLOS III . 2017
JR17/00026 AYUDA JOAN RODÉS DRA. TANIA FLEITAS /2017/322)
Investigador Principal: TANIA CAROLINA FLEITAS KANONNIKOFF
JR17/00026 . INSTITUTO SALUD CARLOS III . 2018
Macrófagos asociados al tumor, angiogénesis tumoral y resistencia a las terapias en Cáncer Gástrico Difuso fenotipo Mesenquimal.
Investigador Principal: TANIA CAROLINA FLEITAS KANONNIKOFF
PI18/01508 . INSTITUTO SALUD CARLOS III . 2019
Medicina personalizada en pacientes con cáncer colorrectal localizado: abordaje multiómico de la Enfermedad Mínima Residual en biopsia líquida y modelos de organoides
Investigador Principal: ANDRÉS CERVANTES RUIPEREZ
PI18/01909 . INSTITUTO SALUD CARLOS III . 2019
Elucidating the contribution of DNA methylation in non-small cell lung cancer.
Investigador Principal: FRANCISCO GIMENO VALIENTE
APOSTD/2021/168 . CONSELLERIA EDUCACION/INNOVACION,UNIVERSIDADES, CIENCIA Y SOCIEDAD DIGITAL/EMPLEO; SOCIEDAD VALENCIANA DE NEFROLOGÍA
Caracterización y abordaje de la enfermedad mínima residual en cáncer de colon localizado: un paso hacia la medicina de precisión.
Investigador Principal: NOELIA TARAZONA LLAVERO
PI21/00689 . INSTITUTO SALUD CARLOS III . 2022
Cita
Papaccio F,Garcia B,Gimeno F,Cabeza M,Gambardella V,Gutierrez MF,Alfaro C,Martinez C,Rentero P,Zuniga S,Carbonell JA,Fleitas T,Rosello S,Huerta M,Sanchez Del Pino MM,Sabater L,Roda D,Tarazona N,Cervantes A,Castillo J. "Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction". J. Exp. Clin. Cancer Res. 2023. 42. (1):p. 8-8. IF:11,400. (1).
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction". Papaccio F, Garcia B, Gimeno F, Cabeza M, Gambardella V, Gutierrez MF, Alfaro C et al. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH. 2023 enero 06. 42 (1):8-8. DOI:10.1186/s13046-022-02591-z. PMID:36604765.
