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Quantitative proteome analysis of plasma microparticles for characterization of HCV-induced hepatic cirrhosis and hepatocellular carcinoma

ABSTRACT: A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS. A quantitative label-free proteome analysis was performed using plasma samples from 22 hepatitis-C virus (HCV)-induced liver cirrhosis patients, 16 HCV-positive hepatocellular carcinoma patients with underlying cirrhosis and 18 healthy controls. Plasma microparticles (PMPS) were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Barbara Sitek

PROVIDER: MSV000085094 | MassIVE | Thu Mar 12 22:43:00 GMT 2020

SECONDARY ACCESSION(S): PXD005777

REPOSITORIES: MassIVE

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Quantitative proteome analysis of plasma microparticles for the characterization of HCV-induced hepatic cirrhosis and hepatocellular carcinoma.

Taleb Raghda Saad Zaghloul RSZ Moez Pacint P Younan Doreen D Eisenacher Martin M Tenbusch Matthias M Sitek Barbara B Bracht Thilo T

Proteomics. Clinical applications 20170710 11-12

<h4>Purpose</h4>Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV-induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiolo ...[more]

PMID: 28626882

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Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens