Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation

Yagmur, Eray; Trautwein, Christian; Leers, Math P.G.; Gressner, A. M.; Tacke, Frank

doi:10.1016/j.clinbiochem.2006.12.010

Cited by 47 publications

(44 citation statements)

References 16 publications

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“…This observation is likely to be explained on the basis that obstruction of the main bile duct with consequent dilatation and epithelial disruption directly influences the balance of proliferation and cell death within the biliary epithelium (Lesage et al, 2001;Alpini et al, 2003). Low-grade cholangitis is quite common following biliary stenting and may also represent an additional confounding factor, as both generalised sepsis (Roth et al, 2004) and cholangitis (Yagmur et al, 2007) raise circulating CK18 concentrations. Other studies have demonstrated significant disturbances in circulating CK18 in patients with chronic liver disease (Hetz et al, 2007;Yagmur et al, 2007).…”

Section: Ck18 In Pancreatic Cancermentioning

confidence: 99%

“…Low-grade cholangitis is quite common following biliary stenting and may also represent an additional confounding factor, as both generalised sepsis (Roth et al, 2004) and cholangitis (Yagmur et al, 2007) raise circulating CK18 concentrations. Other studies have demonstrated significant disturbances in circulating CK18 in patients with chronic liver disease (Hetz et al, 2007;Yagmur et al, 2007).…”

Section: Ck18 In Pancreatic Cancermentioning

confidence: 99%

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

et al. 2010

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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 À80 1C 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 ¼ 19) were found to have greater median (IQR) M65 levels (1145 (739 -1698) U l À1 ) compared with the locally advanced (n ¼ 20; 748 (406 -1150) U l À1 ) and resected (n ¼ 64; 612 (331 -987) U l À1 ) patients (P ¼ 0.002). Elevated M65 levels were associated with poorer overall survival on univariate (Po0.001) but not multivariate (P ¼ 0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum -bilirubin levels (Po0.001) and the duration of plasma storage (Po0.001). 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. Pancreatic ductal adenocarcinoma is a leading cause of cancer deaths (http://www-dep.iarc.fr/) wherein, because of its characteristically late presentation, only 10 -15% of patients present with resectable tumours (Alexakis et al, 2004). For the remaining 85 -90% of patients presenting with inoperable disease, administration of systemic chemotherapy represents the most widely utilised palliative treatment modality (Yip et al, 2006). Conventional chemotherapy regimens incorporating either 5-FU or gemcitabine typically result in only modest improvement in overall survival (Sultana et al, 2007). One of the key challenges in accelerating improved cancer therapeutics is the identification of biomarkers to enable early objective assessment of tumour responses to chemotherapy (Kummar et al, 2007).Necrosis of malignant and normal epithelial cells cause release of cytokeratin 18 (CK18) (Kramer et al, 2004), a type I intermediate filament protein and a component of the intracellular cytoskeleton (Fuchs and Weber, 1994). Caspase-mediated cleavage of the CK18 contributes to the degradation of the intracellular cytoskeleton if epithelial cells undergo apoptosis (Leers et al, 1999). Enzymelinked immunosorbent assays (ELISAs) have been developed to measure circulating concentrations of both full-length CK18 (M65) and caspase-cleaved CK18 fragments (M30) (Kramer et al, 2004). Thus, the M65 ELISA reports necrotic and apoptotic epithelial cell death, whereas the M30 ELISA reports levels of epithelial apoptosis specifically (Kramer et al, 2004). Early studies suggest that these assays ...

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Section: Ck18 In Pancreatic Cancermentioning

confidence: 99%

Section: Ck18 In Pancreatic Cancermentioning

confidence: 99%

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

et al. 2010

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“…Hepatocyte apoptosis and elevated CK-18 fragment levels are also prominent features of cholestatic liver diseases. 10 Furthermore, presumably due to increased cell turnover, elevated serum levels of CK-18 fragments have been reported even in noncirrhotic hepatocellular carcinoma. 10 In conclusion, CK-18 fragments represent a strong predictor and useful noninvasive biomarker for the diagnosis of NASH in well-defined patients.…”

Section: An Apoptosis Biomarker For Prediction Of Nonalcoholic Steatomentioning

confidence: 99%

“…10 Furthermore, presumably due to increased cell turnover, elevated serum levels of CK-18 fragments have been reported even in noncirrhotic hepatocellular carcinoma. 10 In conclusion, CK-18 fragments represent a strong predictor and useful noninvasive biomarker for the diagnosis of NASH in well-defined patients. However, it should be taken into account that a variety of hepatic pathologies may result in elevated CK-18 fragment levels.…”

Section: An Apoptosis Biomarker For Prediction Of Nonalcoholic Steatomentioning

confidence: 99%

An apoptosis biomarker for prediction of nonalcoholic steatohepatitis #

Bantel¹,

Bahr²,

Schulze‐Osthoff³

2009

Hepatology

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“…In some preliminary reports, the M30 assay has been claimed to be both predictive of drug response (Demiray et al, 2006) and prognostic of survival (Ulukaya et al, 2007). The two ELISAs have also been utilized as markers of host tissue toxicity in a number of different clinical conditions including trauma, sepsis (Roth et al, 2004), chronic liver disease (Yagmur et al, 2007), hepatitis C (Bantel et al, 2004) and in liver transplantation (Baskin-Bey et al, 2007).…”

Section: Detection Of Ck Expression In the Diagnosis Of Tumorsmentioning

confidence: 99%

Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18) as Response Markers in Anticancer Therapy

Hamilton¹

2012

Cytokeratins - Tools in Oncology

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Elevated apoptosis-associated cytokeratin 18 fragments (CK18Asp386) in serum of patients with chronic liver diseases indicate hepatic and biliary inflammation

Cited by 47 publications

References 16 publications

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

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

An apoptosis biomarker for prediction of nonalcoholic steatohepatitis #

Cytokeratin 18 (CK18) and Caspase-Cleaved CK18 (ccCK18) as Response Markers in Anticancer Therapy

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