DEK is a potential marker for aggressive phenotype and irinotecan-based therapy response in metastatic colorectal cancer

作者：Martinez Useros Javier; Rodriguez Remirez Maria; Borrero Palacios Aurea; Moreno Irene; Cebrian Arancha; Gomez del Pulgar Teresa; del Puerto Nevado Laura; Vega Bravo Ricardo; Puime Otin Alberto; Perez Nuria; Zazo Sandra; Senin Clara; Fernandez Acenero Maria J; Soengas Maria S; Rojo Federico; Garcia Foncillas Jesus^*

来源：BMC Cancer, 2014, 14(1): 965.

DOI：10.1186/1471-2407-14-965

• DEK
• Irinotecan
• Aggressive phenotype
• Metastatic colorectal cancer
• KRAS

Background: DEK is a transcription factor involved in stabilization of heterochromatin and cruciform structures. It plays an important role in development and progression of different types of cancer. This study aims to analyze the role of DEK in metastatic colorectal cancer.
Methods: Baseline DEK expression was firstly quantified in 9 colorectal cell lines and normal mucosa by WB. SiRNA-mediated DEK inhibition was carried out for transient DEK silencing in DLD1 and SW620 to dissect its role in colorectal cancer aggressiveness. Irinotecan response assays were performed with SN38 over 24 hours and apoptosis was quantified by flow cytometry. Ex-vivo assay was carried out with 3 fresh tumour tissues taken from surgical resection and treated with SN38 for 24 hours. DEK expression was determined by immunohistochemistry in 67 formalin-fixed paraffin-embedded tumour samples from metastatic colorectal cancer patients treated with irinotecan-based therapy as first-line treatment.
Results: The DEK oncogene is overexpressed in all colorectal cancer cell lines. Knock-down of DEK on DLD1 and SW620 cell lines decreased cell migration and increased irinotecan-induced apoptosis. In addition, low DEK expression level predicted irinotecan-based chemotherapy response in metastatic colorectal cancer patients with KRAS wild-type.
Conclusions: These data suggest DEK overexpression as a crucial event for the emergence of an aggressive phenotype in colorectal cancer and its potential role as biomarker for irinotecan response in those patients with KRAS wild-type status.

• 出版日期2014-12-16