Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent progress in mass spectrometry has led to new challenges in glycomics, including the development of rapid glycan enrichment techniques. A facile technique for exploration of a carbohydrate-related biomarker is important because proteomics research targets glycosylation, a posttranslational modification. Here we report an "all-in-one" protocol for high throughput clinical glycomics. This new technique integrates glycoblotting-based glycan enrichment onto the BlotGlycoABC bead, on-bead stabilization of sialic acids, and fluorescent labeling of oligosaccharides in a single workflow on a multiwell filter plate. The advantage of this protocol and MALDI-TOF MS was demonstrated through differentiation of serum N-glycan profiles of subjects with congenital disorders of glycosylation and hepatocellular carcinoma and healthy donors. The method also permitted total cellular glycomics analysis of human prostate cancer cells and normal human prostate epithelial cells. These results demonstrate the potentials of glycan enrichment/processing for biomarker discovery.
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PMID:BlotGlycoABCTM, an integrated glycoblotting technique for rapid and large scale clinical glycomics. 1798 39

This paper presents computational methods to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. The methods are applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD) consisting of cirrhosis and fibrosis cases, and 78 population controls. Two complementary sample preparation methods were applied prior to generating mass spectra: (1) low molecular weight (LMW) enrichment of each serum sample was carried out for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in each serum sample and permethylated for MALDI-TOF quantification of glycans. A peak selection algorithm was applied to identify the most useful peptide and glycan peaks for accurate detection of HCC cases from high-risk population of patients with CLD. In addition to global peaks selected by the whole population based approach, where identically labeled patients are treated as a single group, subgroup-specific peaks were identified by searching for peaks that are differentially abundant in a subgroup of patients only. The peak selection process was preceded by peak screening, where we eliminated peaks that have significant association with covariates such as age, gender, and viral infection based on the peptide and glycan spectra from population controls. The performance of the selected peptide and glycan peaks was evaluated in terms of their ability in detecting HCC cases from patients with CLD in a blinded validation set and through the cross-validation method. Finally, we investigated the possibility of using both peptides and glycans in a panel to enhance the diagnostic capability of these candidate markers. Further evaluation is needed to examine the potential clinical utility of the candidate peptide and glycan markers identified in this study.
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PMID:Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma. 1818 45

We present a computational framework for analysis of MALDI-TOF mass spectrometry data to enable quantitative comparison of glycans in serum. The proposed framework enables a systematic selection of glycan structures that have good generalization capability in distinguishing subjects from two pre-labeled groups. We applied the proposed method for a biomarker discovery study that involves 203 participants from Cairo, Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD), and 78 healthy individuals. Glycans were enzymatically released from proteins in serum and permethylated prior to mass spectrometric quantification. A subset of the participants (35 HCC and 35 CLD cases) was used as a training set to select global and subgroup-specific peaks. The peak selection step is preceded by peak screening, where we eliminate peaks that seem to have association with covariates such as age, gender, and viral infection based on the 78 spectra from healthy individuals. To ensure that the global peaks have good generalization capability, we subjected the entire spectral preprocessing and peak selection step to a cross-validation; a randomly selected subset of the training set was used for spectral preprocessing and peak selection in multiple runs with resubstitution. In addition to global peak identification method, we describe a new approach that allows the selection of subgroup-specific glycans by searching for glycans that display differential abundance in a subgroup of patients only. The performance of the global and subgroup-specific peaks is evaluated via a blinded independent set that comprises of 38 HCC and 17 CLD cases. Further evaluation of the potential clinical utility of the selected global and subgroup-specific candidate markers is needed.
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PMID:Analysis of MALDI-TOF mass spectrometry data for detection of glycan biomarkers. 1822 88

The incidence of hepatocellular carcinoma (HCC) is highest among primary liver cancer. HBV and HBV-induced liver cirrhosis may lead to HCC (1). At present, it is difficult to diagnose HCC at early stage or to differentiate HCC. Therefore, it is much needed to explore and develop a simple, rapid diagnostic method, which has higher sensitivity and specificity for HCC at early stage (2, 3). Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a novel non-electrophoresis-based proteomic technology. SELDI offers the advantages of rapid and simple examination as well as high specificity and sensitivity (4, 5). To our knowledge,there has been little study reported using SELDI-TOF-MS technology to investigate HCC. In this study, 25 cases of HCC patients not receiving any therapy, 25 cases receiving the interposition chemotherapy and 50 cases of the healthy people were tested by Weak cationic exchange (WCX2) protein chip and SELDI-TOF-MS. The differentially expressed peptides or proteins were analyzed by BioMarker Wizard software. At the different M/Z value range, seven peptides/ proteins were obviously different among these three groups. Four peptides including 6489.48Da, 6662.34Da, 8593.75Da and 8720.23Da were up-regulated in healthy controls, two including 7777.27Da and 9250.00Da were up-regulated in the patients with HCC without receiving any therapy and one protein of 16200.17Da was up-regulated in the patients with HCC receiving the interposition chemotherapy. Using Biomarker Pattern software, one pattern including two peptides (7777.27Da, 9250.00Da) can separate HCC without receiving any therapy from normal controls. This diagnosis pattern gave the much-improved sensitivity of 92% and the specificity of 100%. Through searching protein database, these seven peptides or proteins were identified as possible Galanin related peptide, Pro-neuregulin-4 protein, small inducible cytokine A15 precursor, 9 kDa protein, CSL-zincfinger protein 1, mitochondrial hinge protein, actin related protein, respectively. Using SELDI-TOF MS, the method of sieving the tumor markers from HCC becomes quick and valid. These differentially expressed peptides or proteins could be biomarkers of HCC in the serum and drug targets for treating HCC.
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PMID:SELDI-TOF MS proteinchip technology for screening of serum markers of HBV-induced hepatocellular carcinoma. 1836 45

To identify potential oncofetal biomarkers that distinguish hepatocellular carcinoma (HCC) from healthy liver tissues, we compared and analyzed the proteomic profiles of mouse livers at different developmental stages. Fetal (E13.5, E16.5), newborn (NB), postnatal (3-week) and adult (3-month) livers were isolated and profiled by 2-D PAGE. Statistical analysis using linear regression and false discovery rate (FDR) revealed that 361 protein spots showed significant changes. Unsupervised hierarchical tree analysis segregated the proteins into fetal, NB, and postnatal-adult clusters. Distinctive protein markers were identified by MALDI-TOF/MS and the corresponding mRNA profiles were further determined by Q-PCR. Fetal markers (hPCNA, hHSP7C, hHEM6) and postnatal-adult markers (hARGI1, hASSY, hBHMT, hFABPL) were selected for testing against a panel of seven human hepatocyte/HCC cell lines and 59 clinical specimens. The fetal proteins were found to be overexpressed in the metastatic HCC cell lines and the tumor tissues, whereas the postnatal-adult proteins were expressed in non-tumor tissues and normal hepatocytes. This "Ying-Yang" pattern, as orchestrated by distinct fetal and adult markers, is hypothesized to indicate the progressive change of the liver from a growing, less-differentiated organ into a functional metabolic center. Thus, embryogenesis and tumorigenesis share certain oncofetal markers and adult "hepatic" phenotypes are lost in HCC.
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PMID:Comparative proteomic analysis of mouse livers from embryo to adult reveals an association with progression of hepatocellular carcinoma. 1842 28

Many factors play into the complexity of viral pathogenesis. Understanding viral pathogenesis is key to developing vaccines and treatments for viral diseases. One emerging area of research is proteomics, which is the study of the protein complement and functions of the genome. Many different proteomic approaches have been utilized by researchers worldwide to further elucidate viral pathogenesis. For example, a high throughput MALDI-MS approach was recently employed to study the antigenicity of the influenza virus. Another study utilized MALDI-TOF MS and liquid chromatography MS/MS of proteins present in lipid droplets of hepatoma cell lines to identify proteins involved in the pathogenesis of hepatitis C virus that contribute to its carcinogenic properties. In conjugation with MS, yeast two-hybrid systems have also been shown to be useful in identifying potential host receptors of various viruses as well as revealing the interaction of viral proteins with other host proteins and viral proteins. In this review, the focus is on various proteomic approaches to dissecting the mechanisms of viral pathogenesis.
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PMID:Proteomic dissection of viral pathogenesis. 1881 85

Hepatocellular carcinoma (HCC) is a major cause of cancer worldwide and is often characterized by aggressive tumour behaviour and poor prognosis. One of the major etiologies is hepatitis B or C virus (HBV or HCV) infections. In order to better comprehend the molecular mechanisms involved in HCC progression, we performed a systematic analysis on moderately and poorly differentiated human HCC tissues using 2-D DIGE coupled to MALDI-TOF/TOF MS. A total of 52 and 26 proteins were found to be dysregulated in moderately and poorly differentiated HCC tissues, respectively. For the first time, the over-expression of a novel protein family, far upstream binding proteins (FUBPs) was identified in both stages of HCC and confirmed by western blots. FUBPs are of particular interest due to their transcriptional activity on the oncogene, c-myc. It has generally been accepted that c-myc plays an important role in HCC progression but its exact activators remain poorly understood. Interestingly, we also observed elevated c-myc levels in the tissues used in this study by western blot analysis. We therefore propose that the FUBP family of proteins may be one of the possible upstream players that are involved in modulating the c-myc levels in HCC tumorigenesis.
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PMID:2-D DIGE profiling of hepatocellular carcinoma tissues identified isoforms of far upstream binding protein (FUBP) as novel candidates in liver carcinogenesis. 1900 64

Quantitative comparison of peptides and glycans in serum is conducted using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify biomarkers. A peak selection algorithm is developed to identify a panel of integrated peptide and glycan peaks to distinguish hepatocellular carcinoma (HCC) cases from high-risk population of patients with chronic liver disease (CLD). Candidate peptide and glycan markers selected frequently in multiple runs of the algorithm are presented. The performance of these markers is evaluated in terms of their ability to distinguish HCC cases from patients with CLD in a blinded validation set.
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PMID:Integrated peptide and glycan biomarker discovery using MALDI-TOF mass spectrometry. 1916 37

Lack of sensitive and specific biomarkers is a major reason for the high rate of hepatocellular carcinoma (HCC) related mortality. The aim of this study was to use surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS) technology to identify potential protein patterns specific for HCC. Eighty-one patients with hepatitis B-related HCC and 80 healthy controls were randomly divided into a training set (48 HCC, 47 controls) and a testing set (33 HCC, 33 controls). Serum proteomic profiles were measured using SELDI-TOF-MS. A classification tree was established by Biomarker Pattern Software. Candidate biomarkers were separated by HPLC and identified by MALDI-MS/MS and database searching. Forty-eight HCC cases, 54 liver cirrhosis cases and 42 healthy people were clinically validated using candidate biomarkers by SELDI-Immunoassay. Two up-regulated protein peaks were automatically chosen as a classification tree in the training set. These biomarkers were identified as thrombin light chain and growth related oncogene-alpha (GRO-alpha). The sensitivity and specificity of this classification tree were 89.6%. The multivariate model using the two biomarkers and AFP resulted in a sensitivity of 91.7% and specificity of 92.7%, which was significantly better than that of alpha-fetoprotein alone. We conclude that thrombin light chain and GRO-alpha are potential biomarkers of HCC.
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PMID:Identifying serological biomarkers of hepatocellular carcinoma using surface-enhanced laser desorption/ionization-time-of-flight mass spectroscopy. 1926 39

To discover new potential biomarkers of HCC, we used 2-DE gel separation and MALDI-TOF-MS analysis of partially enriched nuclear fractions from liver biopsies of 20 different patients. We obtained a proteomic map of subfractioned liver samples including about 200 common protein spots, among which identified components corresponded to expression products of 52 different genes. A differential analysis of proteins from tumoral and control tissues revealed a significant change in the expression level of 16 proteins associated to cytoskeletal, stress response and metabolic functions. These data may provide novel candidate biomarkers for HCC and useful insights for understanding the mechanisms of HCC pathogenesis and progression.
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PMID:Differential proteomic analysis of subfractioned human hepatocellular carcinoma tissues. 1929 Jun 26


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