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

ABSTRACT: 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.Plasma samples from 103 patients with pancreatic cancer stored at -80 degrees 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).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.

SUBMITTER: Dive C

PROVIDER: S-EPMC2822934 | biostudies-other | 2010 Feb

REPOSITORIES: biostudies-other

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Project description:BackgroundPancreatic cancer (PC) has a dismal prognosis due to its insidious early symptoms and poor early detection rate. Exosomes can be released by various cell types and tend to be a potential novel biomarker for PC detection. In this study, we explored the proteomic profiles of plasma exosomes collected from patients with PC at different stages and other pancreatic diseases.MethodsPlasma samples were collected from six groups of patients, including PC at stage I/II, PC at stage III/IV, well-differentiated pancreatic neuroendocrine tumor (P-NET), pancreatic cystic lesions (PCLs), chronic pancreatitis (CP), and healthy controls (HCs). Plasma-derived exosomes were isolated by ultracentrifugation and identified routinely. Isobaric tags for relative and absolute quantification (iTRAQ) based proteomic analysis along with bioinformatic analysis were performed to elucidate the biological functions of proteins. The expression of exosomal ALIX was further confirmed by enzyme-linked immunosorbent assay in a larger cohort of patients. Furthermore, receiver operating characteristic curve analysis was applied to evaluate the potential of ALIX as a novel diagnostic biomarker.ResultsThe proteomic profile revealed a total of 623 proteins expressed among the six groups, and 16 proteins with differential degrees of abundance were found in PC vs. other pancreatic diseases (including P-NET, PCLs, and CP). Based on the results of proteomic and bioinformatic analyses, exosomal ALIX was subsequently selected as a novel biomarker for PC detection and validated in another clinical cohort. We noticed that ALIX expression was elevated in PC patients compared with patients with other pancreatic diseases or HC, and it was also closely associated with TNM stage and distant metastasis. Interestingly, the combination of exosomal ALIX and serum CA199 has greater values in differentiating both early vs. late PC (AUC value 0.872) and PC vs. other pancreatic diseases (AUC value 0.910) than either ALIX or CA199 alone.ConclusionIn summary, our study demonstrated that based on proteomic profiling, proteins isolated from the plasma-derived exosomes may function as ideal non-invasive biomarkers for the clinical diagnosis of PC. Importantly, exosomal ALIX combined with CA199 has great potentials in detection of PC, especially in distinguishing PC patients at early stages from advanced stages.

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

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