Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

Background:

Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer.

Methods:

Plasma samples from 103 patients with pancreatic cancer stored at −80 °C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23–57) months. Patients with metastatic disease (n=19) were found to have greater median (IQR) M65 levels (1145 (739–1698) U l⁻¹) compared with the locally advanced (n=20; 748 (406–1150) U l⁻¹) and resected (n=64; 612 (331–987) U l⁻¹) patients (P=0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P<0.001) but not multivariate (P=0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum–bilirubin levels (P<0.001) and the duration of plasma storage (P<0.001).

Conclusions:

Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors.