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Proteomic profiling of hepatitis B virus-related hepatocellular carcinoma in China: a SELDI-TOF-MS study.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality, but its underlying molecular mechanisms remain not well understood. High-throughput, proteomic techniques targeting unique biological molecules may provide novel insights into HCC pathogenesis and prognosis. In this study, we systemically investigated tissue biomarkers of HCC by using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technique. Proteomic spectra were generated from fresh tissues (26 HCC and 18 control cirrhotic liver) and analyzed by using Biomarker Wizard System. A total of 16 differential proteomic peaks were detected between HCC and cirrhotic liver tissues, and 11 between moderately and highly differentiated HCCs. The expression pattern of one proteomic peak was validated by immunohistochemistry. These molecules are potential candidate biomarkers for early diagnosis of and targeted therapy for HCC.

SUBMITTER: Zhang J

PROVIDER: S-EPMC2480544 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Proteomic profiling of hepatitis B virus-related hepatocellular carcinoma in China: a SELDI-TOF-MS study.

Zhang Jianzhong J Li Dong D Zheng Yanhua Y Cui Yan Y Feng Kai K Zhou Jinlian J Wu Jihua J

International journal of clinical and experimental pathology 20080101 4

Hepatocellular carcinoma (HCC) is one of the most common malignancies with high mortality, but its underlying molecular mechanisms remain not well understood. High-throughput, proteomic techniques targeting unique biological molecules may provide novel insights into HCC pathogenesis and prognosis. In this study, we systemically investigated tissue biomarkers of HCC by using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technique. Proteomic spect ...[more]

PMID: 18787613

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Project description:The metabolic pathway disturbances associated with hepatocellular carcinoma (HCC) remain unsatisfactorily characterized. Determination of the metabolic alterations associated with the presence of HCC can improve our understanding of the pathophysiology of this cancer and may provide opportunities for improved disease monitoring of patients at risk for HCC development. To characterize the global metabolic alterations associated with HCC arising from hepatitis C (HCV)-associated cirrhosis using an integrated non-targeted metabolomics methodology employing both gas chromatography/mass spectrometry (GC/MS) and ultrahigh-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/MS-MS).The global serum metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30 healthy volunteers were characterized using a metabolomics approach that combined two metabolomics platforms, GC/MS and UPLC/MS-MS. Random forest, multivariate statistics and receiver operator characteristic analysis were performed to identify the most significantly altered metabolites in HCC patients vs. HCV-cirrhosis controls and which therefore exhibited a close association with the presence of HCC.Elevated 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, sphingosine, ?-glutamyl oxidative stress-associated metabolites, xanthine, amino acids serine, glycine and aspartate, and acylcarnitines were strongly associated with the presence of HCC. Elevations in bile acids and dicarboxylic acids were highly correlated with cirrhosis.Integrated metabolomic profiling through GC/MS and UPLC/MS-MS identified global metabolic disturbances in HCC and HCV-cirrhosis. Aberrant amino acid biosynthesis, cell turnover regulation, reactive oxygen species neutralization and eicosanoid pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced bile acid metabolism and elevations in fibrinogen cleavage peptides may be signatures of cirrhosis.

Project description:Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ?10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.

Dataset Information

Proteomic profiling of hepatitis B virus-related hepatocellular carcinoma in China: a SELDI-TOF-MS study.

Publications

Proteomic profiling of hepatitis B virus-related hepatocellular carcinoma in China: a SELDI-TOF-MS study.

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