Schwegler EE, Cazares L, Steel LF, Adam B-L, Johnson DA, Semmes OJ, Block TM, Marrero JA, Drake RRSELDI-TOF MS profiling of serum for detection of the progression of chronic hepatitis C to hepatocellular carcinoma. Hepatology 41: 634-642

Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia, United States
Hepatology (Impact Factor: 11.06). 03/2005; 41(3):634-42. DOI: 10.1002/hep.20577
Source: PubMed


Proteomic profiling of serum is an emerging technique to identify new biomarkers indicative of disease severity and progression. The objective of our study was to assess the use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify multiple serum protein biomarkers for detection of liver disease progression to hepatocellular carcinoma (HCC). A cohort of 170 serum samples obtained from subjects in the United States with no liver disease (n = 39), liver diseases not associated with cirrhosis (n = 36), cirrhosis (n = 38), or HCC (n = 57) were applied to metal affinity protein chips for protein profiling by SELDI-TOF MS. Across the four test groups, 38 differentially expressed proteins were used to generate multiple decision classification trees to distinguish the known disease states. Analysis of a subset of samples with only hepatitis C virus (HCV)-related disease was emphasized. The serum protein profiles of control patients were readily distinguished from each HCV-associated disease state. Two-way comparisons of chronic hepatitis C, HCV cirrhosis, or HCV-HCC versus healthy had a sensitivity/specificity range of 74% to 95%. For distinguishing chronic HCV from HCV-HCC, a sensitivity of 61% and a specificity of 76% were obtained. However, when the values of known serum markers alpha fetoprotein, des-gamma carboxyprothrombin, and GP73 were combined with the SELDI peak values, the sensitivity and specifity improved to 75% and 92%, respectively. In conclusion, SELDI-TOF MS serum profiling is able to distinguish HCC from liver disease before cirrhosis as well as cirrhosis, especially in patients with HCV infection compared with other etiologies.

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Available from: Oliver John Semmes, Sep 18, 2014
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    • "The area under the receiver-operating characteristic curve (AUROC) was 0.9. Gu et GP73 expression in HCC 878 Int J Clin Exp Pathol 2012;5(9):874-881 al [21] concluded that GP73 concentrations in patients with liver disease were three-fold higher than in healthy individuals. However, GP73 concentrations did not differ significantly between patients in each liver disease group. "
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    ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and its incidence has been increasing worldwide. Serum alpha-fetoprotein (AFP) levels and abdominal ultrasound have been widely used for diagnosis as well as surveillance of HCC. However, the sensitivity and specificity of both AFP levels and ultrasound for HCC surveillance have some shortcomings, particularly in the early stages of the disease. Golgi protein-73 (GP73) is a type II Golgi-localized integral membrane protein that is normally expressed in epithelial cells of many human tissues. It is essential for human survival, and might have multiple roles for GP73 in epithelial cell function such as in the kidney and liver. However, details of its biochemical function and regulation of GP73 expression are unknown at present. GP73 expression is upregulated in serum samples from patients with liver disease, with expression being highest in HCC. Therefore, it may be useful as a new serum marker for detection of HCC in at high-risk population. But, this hypothesis needs to be proven in large cohorts.
    Preview · Article · Nov 2012 · International journal of clinical and experimental pathology
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    • "Analysis of proteomic patterns by mass spectrometry (MS) is a relatively novel approach for the identification of potential biomarkers associated with various diseases [8]. Surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been previously applied to predict hepatic fibrosis or cirrhosis in patients with CHB [9] [10] and to detect the progression of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC) [11]. More recently, magnetic bead-based affinity purification with subsequent matrixassisted laser desorption/ionization time-of-flight mass spectrometry Clinica Chimica Acta 412 (2011) 2174–2182 Abbreviations: AE, acute exacerbation; APOA4, apolipoprotein A-IV; APP, acutephase proteins; CHB, chronic hepatitis B; CHC, chronic hepatitis C; FGA, fibrinogen α chain; FGB, fibrinogen β chain; HCCA, alpha-cyano-4-hydroxycinnamic acid; HNF, hepatocyte nuclear factor; KNG1, kininogen-1; LIFT, laser-induced fragmentation technology; HIC, hydrophobic interaction chromatography; IMAC, immobilized metal ion affinity chromatography ; SOM, self-organizing map; TFA, trifluoacetic acid; TTR, transthyretin. "
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    ABSTRACT: Acute exacerbations (AE) of serum alanine aminotransferase activities that are 5 times above the normal upper limit frequently occur during the immune clearance phase of hepatitis Be antigen (HBeAg)-positive chronic hepatitis B (CHB). It is unclear how the varying clinical severities of AE reflect differences in the underlying immune responses against the hepatitis B virus. We utilized magnetic bead-based purification methods coupled with MALDI-TOF mass spectrometry to generate plasma peptide profiles from HBeAg-positive CHB patients experiencing AE without and with clinical decompensation. Hydrophobic interaction chromatography (HIC C18) provided a more discriminatory spectral profile than immobilized Cu(2+) metal ion affinity chromatography did for diagnosis of a clinical spectrum of AEs. Using the sorting algorithm, Support Vector Machine, a classification model consisting of 5 classifiers was determined to give a sensitivity of 94.7% and a specificity of 75% for differentiating patients with and without decompensation. Classifiers identified as fragments derived from transthyretin and apolipoprotein A-IV were significantly decreased and increased in patients with decompensation, respectively. Our study demonstrated that HIC C18 fractionation coupled with MALDI-TOF mass spectrometry can be used for differentiating AE with and without decompensation in patients with HBeAg-positive CHB.
    Full-text · Article · Aug 2011 · Clinica chimica acta; international journal of clinical chemistry
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    • "Until now, the most commonly used instrument was the SELDI-TOF MS. This technology has been used successfully to discover potential serum diagnostic markers for breast [6], lung [7], bladder [8], liver [9], and gastric [10]cancers. After the original highly intriguing report that the serum proteome profile can be used for the early detection of ovarian cancer, many researchers have applied the SELDI-TOF MS technology to detect proteome profiles specific for other forms of cancer and non-malignant disease. "
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