Circulating tumor cells (CTC) and KRAS mutant circulating free DNA (cfDNA) detection in peripheral blood as biomarkers in patients diagnosed with exocrine pancreatic cancer

BMC Cancer

Research Article

Jose Carlos Martinez-Avila¹  Núria Malats¹  Julie Earl²  Sandra Garcia-Nieto²  Carmen Guillen-Ponce²  Mercedes Rodríguez-Garrote²  Alfredo Carrato²  José Montans³  Eduardo Lobo⁴  Elena Mendía⁴  Alfonso Sanjuanbenito⁴  Eduardo Lisa⁴ 

[1] Genetic and Molecular Epidemiology Group, Spanish Cancer Research Cancer Center, Madrid, Spain;Medical Oncology Department, Ramón y Cajal University Hospital, Carretera de Colmenar Viejo, KM 9,100, 28034, Madrid, Spain;Pathology Department, Ramón y Cajal University Hospital, Madrid, Spain;Surgery Department, Ramón y Cajal University Hospital, Madrid, Spain;

关键词: Circulating Free DNA;    KRAS mutation;    Circulating Tumor Cells;    PDAC;    Prognostic Marker;   

DOI  :  10.1186/s12885-015-1779-7

 received in 2015-01-25, accepted in 2015-10-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months.MethodsWe present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC.ResultsWe detected KRAS mutant cfDNA in 26 % of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95 % CI: 19–317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95 % CI: 416–1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95 % CI: 27–206) CTC positive vs 393 days CTC negative (95 % CI: 284–501), CTC were detected in only 20 % of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease.ConclusionsTumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.

【 授权许可】

CC BY   
© Earl et al. 2015