Multi-level evidence that circulating CK18 is a biomarker of tumour burden in colorectal cancer.
Br J Cancer
; 107(9): 1518-24, 2012 Oct 23.
Article
en En
| MEDLINE
| ID: mdl-22996610
ABSTRACT
BACKGROUND:
Circulating total cytokeratin 18 (tCK18) and/or caspase cleaved cytokeratin 18 (cCK18) (measured by M65 and M30 enzyme-linked immunosorbent assays (ELISAs), respectively) are used as pharmacodynamic (PD) biomarkers of epithelial cell death in clinical trials. Having validated these ELISAs, we assessed their utility in colorectal cancer (CRC).METHODS:
We applied the assays in several settings 53 controls; 97 patients undergoing surgery and 74 patients with metastatic CRC undergoing chemotherapy (55 first line; 56 patients with repeated sampling through chemotherapy). Prognostic significance was evaluated using Kaplan-Meier life tables and Cox models; PD utility was assessed by analysis of repeated measures.RESULTS:
Median cCK18 and tCK18 levels were elevated in patients with cancer (both P=0.0001), and among cancer patients, there were increasing trends from early to advanced stages (both P(trends)=0.0001). Increasing tCK18 predicted for reduced survival after surgery with curative intent (adjusted hazard ratio (HR) for doubling in concentration 1.77, 95% CI 1.04, 3.01) and after first-line chemotherapy in metastatic disease (adjusted HR per doubling in concentration=1.78, 95% CI 1.37, 2.30). In patients with progressive disease during chemotherapy, repeated sampling revealed profiles with high baselines and progressive upwardly increases after cycle 1.CONCLUSION:
This study provides evidence for cytokeratin 18 (CK18) as a prognostic and PD biomarker in patients with CRC and supports continued deployment of circulating CK18 in biomarker-enhanced trials.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
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Biomarcadores de Tumor
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Queratina-18
Tipo de estudio:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2012
Tipo del documento:
Article
País de afiliación:
Reino Unido