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Cancers (Basel). 2019 Oct 11;11(10). pii: E1540. doi: 10.3390/cancers11101540.

Tumor Expression of Cyclin-Dependent Kinase 5 (Cdk5) Is a Prognostic Biomarker and Predicts Outcome of Oxaliplatin-Treated Metastatic Colorectal Cancer Patients.

Ruiz de Porras V1,2, Bystrup S3,4, Cabrero-de Las Heras S5,6, Musulén E7,8, Palomero L9,10, Alonso MH11,12,13,14, Nieto R15, Arango D16, Moreno V17,18,19,20, Queralt C21,22, Manzano JL23,24,25, Layos L26,27,28, Bugés C29,30,31, Martinez-Balibrea E32,33.

Author information

1
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. vruiz@igtp.cat.
2
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. vruiz@igtp.cat.
3
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. sbystrup@igtp.cat.
4
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. sbystrup@igtp.cat.
5
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. scabrero@igtp.cat.
6
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. scabrero@igtp.cat.
7
Department of Pathology, Hospital Universitari Germans Trias i Pujol, Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. emusulen@hotmail.com.
8
Department of Pathology, Hospital Universitari General de Catalunya, Grupo Quirónsalud, Pedro i Pons 1, 08195 Sant Cugat del Valles, Spain. emusulen@hotmail.com.
9
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, 08908 L'Hospitalet del Llobregat, Barcelona, Spain. lpalomero@iconcologia.net.
10
ONCOBELL Program, Bellvitge Institute for Biomedical Research, 08908 L'Hospitalet del Llobregat, Barcelona, Spain. lpalomero@iconcologia.net.
11
ONCOBELL Program, Bellvitge Institute for Biomedical Research, 08908 L'Hospitalet del Llobregat, Barcelona, Spain. mhalonso@iconcologia.net.
12
Oncology Data Analytics Program, Institut Català d'Oncologia (ICO), 08908 Barcelona, Spain. mhalonso@iconcologia.net.
13
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain. mhalonso@iconcologia.net.
14
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08907 Barcelona, Spain. mhalonso@iconcologia.net.
15
Group of Biomedical Research in Digestive Tract Tumors, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain. rocio.nieto@vhir.org.
16
Group of Biomedical Research in Digestive Tract Tumors, CIBBIM-Nanomedicine, Vall d'Hebron University Hospital, Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig Vall d'Hebron, 119-129, 08035 Barcelona, Spain. diego.arango@vhir.org.
17
ONCOBELL Program, Bellvitge Institute for Biomedical Research, 08908 L'Hospitalet del Llobregat, Barcelona, Spain. v.moreno@iconcologia.net.
18
Oncology Data Analytics Program, Institut Català d'Oncologia (ICO), 08908 Barcelona, Spain. v.moreno@iconcologia.net.
19
Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain. v.moreno@iconcologia.net.
20
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08907 Barcelona, Spain. v.moreno@iconcologia.net.
21
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. cqueralt@iconcologia.net.
22
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. cqueralt@iconcologia.net.
23
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. jmanzano@iconcologia.net.
24
Medical Oncology Service, Catalan Institute of Oncology (ICO), 08908, Spain. jmanzano@iconcologia.net.
25
B-ARGO group, Germans Trias I Pujol Research Institute (IGTP), Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. jmanzano@iconcologia.net.
26
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. llayos@iconcologia.net.
27
Medical Oncology Service, Catalan Institute of Oncology (ICO), 08908, Spain. llayos@iconcologia.net.
28
B-ARGO group, Germans Trias I Pujol Research Institute (IGTP), Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. llayos@iconcologia.net.
29
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. cbuges@iconcologia.net.
30
Medical Oncology Service, Catalan Institute of Oncology (ICO), 08908, Spain. cbuges@iconcologia.net.
31
B-ARGO group, Germans Trias I Pujol Research Institute (IGTP), Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. cbuges@iconcologia.net.
32
Program of predictive and personalized cancer medicine (PMPPC) Germans Trias i Pujol Research Institute (IGTP), Ctra. Can Ruti-Camí de les escoles s/n, 08916 Badalona, Spain. embalibrea@iconcologia.net.
33
Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, Ctra. Can Ruti- Camí de les escoles s/n, 08916 Badalona, Spain. embalibrea@iconcologia.net.

Abstract

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.

KEYWORDS:

colorectal cancer; cyclin-dependent kinase 5 (Cdk5); oxaliplatin; prognostic and predictive biomarker

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