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

细胞周期蛋白依赖性激酶 5 (Cdk5) 的肿瘤表达是一种预后生物标志物,可预测接受奥沙利铂治疗的转移性结直肠癌患者的预后

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作者:Vicenç Ruiz de Porras, Sara Bystrup, Sara Cabrero-de Las Heras, Eva Musulén, Luis Palomero, Maria Henar Alonso, Rocio Nieto, Diego Arango, Víctor Moreno, Cristina Queralt, José Luis Manzano, Laura Layos, Cristina Bugés, Eva Martinez-Balibrea

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.

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