Sistema de Salut de Catalunya
[Ruiz de Porras V, Bystrup S, Cabrero-de Las Heras S] Program of predictive and personalized cancer medicine (PMPPC), Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain. Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Badalona, Spain. [Musulén E] Department of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. Department of Pathology, Hospital Universitari General de Catalunya, Grupo Quirónsalud, Sant Cugat del Valles, Spain. [Palomero L] Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, L’Hospitalet del Llobregat, Spain. ONCOBELL Program, Bellvitge Institute for Biomedical Research, L’Hospitalet del Llobregat, Spain. [Henar Alonso M] ONCOBELL Program, Bellvitge Institute for Biomedical Research, L’Hospitalet del Llobregat, Spain. Oncology Data Analytics Program, Institut Català d’Oncologia (ICO), Barcelona, Sapin. Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain. Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain. [Nieto R, Arango D] Grup de Recerca en Investigació Biomèdica en Tumors de l'Aparell Digestiu, CIBBIM-Nanomedicine, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2020-09-02T08:04:20Z
2020-09-02T08:04:20Z
2019-10-11
Colorectal cancer; Cyclin-dependent kinase 5 (Cdk5); Prognostic and predictive biomarker
Cáncer colorrectal; Quinasa dependiente de ciclina 5 (Cdk5); Biomarcador pronóstico y predictivo
Càncer colorectal; Quinasa dependent de ciclina 5 (CDK5); Biomarcador pronòstic i predictiu
In recent years, an increasing number of studies have shown that elevated expression of cyclin dependent kinase (Cdk5) contributes to the oncogenic initiation and progression of many types of cancers. In this study, we investigated the expression pattern of Cdk5 in colorectal cancer (CRC) cell lines and in a large number of tumor samples in order to evaluate its relevance in this pathogenesis and possible use as a prognostic marker. We found that Cdk5 is highly expressed and activated in CRC cell lines and that silencing of the kinase decreases their migration ability. In tumor tissues, Cdk5 is overexpressed compared to normal tissues due to a copy number gain. In patients with localized disease, we found that high Cdk5 levels correlate with poor prognosis, while in the metastatic setting, this was only the case for patients receiving an oxaliplatin-based treatment. When exploring the Cdk5 levels in the consensus molecular subtypes (CMS), we found the lowest levels in subtype 1, where high Cdk5 again was associated with a poorer prognosis. In conclusion, we confirm that Cdk5 is involved in CRC and disease progression and that it could serve as a prognostic and predictive biomarker in this disease.
This work has been funded by the ISCIII grants from the Spanish Government, project numbers PI09/01334 and PI12/02228, and the Departament d’Innovació, Universitats i Empresa, Generalitat de Catalunya, project numbers 2014-SGR-1494, 2017-SGR-1705 and 2017-SGR-723. The group from Eva Martinez Balibrea is furthermore funded by the PIE16/00011 and the group from Diego Arango by the PI16/00540 and AC15/00066 grants.
Article
Versió publicada
Anglès
Recte - Càncer; Quinases dependents de ciclina; Marcadors tumorals; DISEASES::Digestive System Diseases::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Digestive System Diseases::Digestive System Diseases::Digestive System Diseases::Digestive System Diseases::Colorectal Neoplasms; CHEMICALS AND DRUGS::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine Kinases::Proline-Directed Protein Kinases::Cyclin-Dependent Kinases::CDC2-CDC28 Kinases::Cyclin-Dependent Kinase 5; CHEMICALS AND DRUGS::Biological Factors::Biomarkers::Biomarkers, Tumor; ENFERMEDADES::enfermedades del sistema digestivo::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::enfermedades del sistema digestivo::enfermedades del sistema digestivo::enfermedades del sistema digestivo::enfermedades del sistema digestivo::neoplasias colorrectales; COMPUESTOS QUÍMICOS Y DROGAS::enzimas y coenzimas::enzimas::transferasas::fosfotransferasas::fosfotransferasas (grupo alcohol aceptor)::proteína cinasas::proteína-serina-treonina cinasas::proteínas cinasas dirigidas por prolina::cinasas dependientes de ciclina::cinasas CDC2-CDC28::cinasa 5 dependiente de la ciclina; COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores::marcadores tumorales
MDPI
Cancers;11(10)
https://www.mdpi.com/2072-6694/11/10/1540
info:eu-repo/grantAgreement/ES/6PN/PI12%2F02228
info:eu-repo/grantAgreement/ES/6PN/PI09%2F01334
info:eu-repo/grantAgreement/ES/PE2013-2016/PI16%2F00540
info:eu-repo/grantAgreement/ES/PE2013-2016/PIE16%2F00011
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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