Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18–Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. METHODS: Soluble plasma CK18–Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18–Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P=0.015, P<0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P=0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18–Asp396 did not reach significance (P=0.01, and P=0.07, respectively). CONCLUSION: Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy.