TY - JOUR
T1 - Tumor expression of cyclin-dependent kinase 5 (Cdk5) is a prognostic biomarker and predicts outcome of oxaliplatin-treated metastatic colorectal cancer patients
AU - de Porras, Vicenç Ruiz
AU - Bystrup, Sara
AU - Las Heras, Sara Cabrero De
AU - Musulén, Eva
AU - Palomero, Luis
AU - Alonso, Maria Henar
AU - Nieto, Rocio
AU - Arango, Diego
AU - Moreno, Víctor
AU - Queralt, Cristina
AU - Manzano, José Luis
AU - Layos, Laura
AU - Bugés, Cristina
AU - Martinez-Balibrea, Eva
PY - 2019/10/1
Y1 - 2019/10/1
N2 - © 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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.
AB - © 2019 by the authors. Licensee MDPI, Basel, Switzerland. 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.
KW - Colorectal cancer
KW - Cyclin-dependent kinase 5 (Cdk5)
KW - Oxaliplatin
KW - Prognostic and predictive biomarker
U2 - 10.3390/cancers11101540
DO - 10.3390/cancers11101540
M3 - Article
C2 - 31614664
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
M1 - 1540
ER -
