NEW YORK (Reuters Health) May 26 - Increasing levels of proteasome are an indicator that cirrhosis is transforming into hepatocellular carcinoma (HCC), French researchers report in the June issue of Gut.
Furthermore, they propose, proteasome inhibitors may be effective anticancer treatment in patients with cirrahosis and changing levels of the proteolytic entity.
Dr. L. Henry and colleagues at the University of Montpellier measured plasma proteasome and alpha-fetoprotein (AFP) levels in 83 patients with cirrhosis, 50 of whom had HCC and 33 who did not, and 40 controls.
"Plasma proteasome levels were significantly higher in patients with HCC than controls," with mean levels of 4841 ng/mL and 2534 ng/mL, respectively, Dr. Henry and colleagues report.
Patients with cirrhosis without HCC had a mean proteasome level of 2077 ng/mL.
Patients with HCC were categorized into three groups according to tumor mass, and even those with low tumor mass had elevated proteasome levels, with a mean level of 3970 ng/mL.
"With a cut-off of 2900 ng/mL, diagnostic specificity for HCC was 97% with a sensitivity of 72%, better than results obtained with AFP," the team reports.
"Diagnostic relevance of plasma proteasome measurement was also effective in low tumor mass patients," with a sensitivity of 76.2% compared with a sensitivity of 57.1% for AFP.
"Plasma proteasome is a novel and relevant marker of HCC, namely for early detection of HCC in patients with cirrhosis," the authors write. "Plasma proteasome levels were independent of the cause of cirrhosis and were weakly correlated with AFP levels."
They note that proteasome inhibitors are a new class of anticancer agents, and have been shown to be effective in conjunction with TNF-related apoptosis-inducing ligand (TRAIL) in models of HCC. "This therapeutic relevance reinforces the hypothesis that proteasome plays a crucial role in HCC onset and development," Dr. Henry and colleagues propose.
Gut 2009;58:833-838.
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