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      Serum peptidome patterns of hepatocellular carcinoma based on magnetic bead separation and mass spectrometry analysis

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          Abstract

          Background

          Hepatocellular carcinoma (HCC) is one of the most common cancers in the world,and the identification of biomarkers for the early detection is a relevant target. The purpose of the study is to discover specific low molecular weight (LMW) serum peptidome biomarkers and establish a diagnostic pattern for HCC.

          Methods

          We undertook this pilot study using a combined application of magnetic beads with Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) technique and ClinPro Tools v2.2 to detect 32 patients with HCC, 16 patients with chronic hepatitis (CH), 16 patients with liver cirrhosis (LC) and 16 healthy volunteers.

          Results

          The results showed 49, 33 and 37 differential peptide peaks respectively appeared in HCC, LC and CH groups. A Supervised Neural Network (SNN) algorithm was used to set up the classification model. Eleven of the identified peaks at m/z 5247.62, 7637.05, 1450.87, 4054.21, 1073.37, 3883.64, 5064.37, 4644.96, 5805.51, 1866.47 and 6579.6 were used to construct the peptides patterns. According to the model, we could clearly distinguish between HCC patients and healthy controls as well as between LC or CH patients and healthy controls.

          Conclusions

          The study demonstrated that a combined application of magnetic beads with MALDI-TOF MB technique was suitable for identification of potential serum biomarkers for HCC and it is a promising way to establish a diagnostic pattern.

          Virtual slides

          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1503629821958720.

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          Most cited references27

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          Management of hepatocellular carcinoma.

          Jordi Bruix, Morris Sherman (2005)
          Article 0 comments Cited 1332 times – based on 0 reviews     Review now
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            Hepatocellular carcinoma: recent trends in the United States.

            Hashem El-Serag (2004)
            Hepatocellular carcinoma (HCC) is increasing in frequency in the United States. The age-adjusted incidence rates have doubled over the past 2 decades. Similar increases have affected the mortality and hospitalization rates. Although there has been a small recent improvement in survival, it remains generally dismal (median, 8 months). It is estimated that 8500 to 11,500 new cases of HCC occur annually in the United States. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age, 65 years) population, there has been a shift toward relatively younger age cases. Men are affected 3 times more frequently than women, Asians are affected 2 times more than blacks, and Hispanics are affected 2 times more often than whites. However, the recent increase has disproportionately affected white (and Hispanic) men between ages 45 and 65 years. The temporal changes of risk factors among HCC cases in the United States remain unclear. However, available studies indicate that hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely to continue to increase for the next decade. A variable but significant proportion of cases (15% to 50%) do not have evidence of the risk factors of viral hepatitis or heavy alcohol consumption. The insulin resistance syndrome, manifesting as obesity and diabetes, is emerging as a risk factor for HCC in the United States; however, its impact on the current trend in HCC remains unclear.
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              A decade's studies on metastasis of hepatocellular carcinoma.

              Xue Ji, Quan Wu, Jia Fan … (2004)
              Metastasis remains one of the major challenges before hepatocellular carcinoma (HCC) is finally conquered. This paper summarized a decade's studies on HCC metastasis at the Liver Cancer Institute of Fudan University. We have established a stepwise metastatic human HCC model system, which included a metastatic HCC model in nude mice (LCI-D20), a HCC cell line with high metastatic potential (MHCC97), a relatively low metastatic potential cell clone (MHCC97L) and several stepwise high metastatic potential cell clones (MHCC97H, HCCLM3, and HCCLM6) from their parent MHCC97 cell. Endeavors have been made for searching human HCC metastasis-related chromosomes/proteins/genes. Monogene-based studies revealed that HCC invasion/metastasis was similar to that of other solid tumors, and the biological characteristics of small HCC were only slightly better than that of large HCC. Using comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), genotyping, cDNA microarray, and 2-dimensional gel electrophoresis, we obtained some interesting results. In particular, in collaboration with the National Institute of Health (NIH) in the United States, we generated a molecular signature that can classify metastatic HCC patients, identified osteopontin as a lead gene in the signature, and found that genes favoring metastasis progression were initiated in the primary tumors. We also found that chromosome 8p deletion, particularly in the region of 8p23, was associated with HCC metastasis. Cytokeratin 19 was identified as one of the proteins, which was found in MHCC97H, but not in MHCC97L cells. Experimental interventions using the high metastatic nude mice model have provided clues for the prevention of HCC metastasis. Translation from workbench to bedside demonstrated that serum VEGF, microvessel density, and p53 scoring may be of value for the prediction of postoperative metastatic recurrence. Interferon alpha proved effective for the prevention of recurrence both experimentally and clinically. In conclusion, HCC metastasis that probably initiated in the primary tumor is a multigene-involved, multistep, and changing process. The further elucidation of the mechanism underlying HCC metastasis will provide a more solid basis for the prediction and prevention of the metastatic recurrence of HCC.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Diagn Pathol
                Journal ID (iso-abbrev): Diagn Pathol
                Title: Diagnostic Pathology
                Publisher: BioMed Central
                ISSN (Electronic): 1746-1596
                Publication date Collection: 2013
                Publication date (Electronic): 5 August 2013
                Volume: 8
                Page: 130
                Affiliations
                [1 ]Department of Medical Oncology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shannxi, PR China
                Article
                Publisher ID: 1746-1596-8-130
                DOI: 10.1186/1746-1596-8-130
                PMC ID: 3751178
                PubMed ID: 23915185
                SO-VID: 37af29df-ee76-4a97-92bf-e07d1b551a14
                Copyright © Copyright ©2013 Ying et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 2 April 2013
                Date accepted : 23 July 2013
                Categories
                Subject: Research

                ScienceOpen disciplines: Pathology
                Keywords: hepatocellular carcinoma,chronic hepatitis,liver cirrhosis,magnetic beads,matri-assisted laser desorption/ionization time-of-flight mass spectrometry,serum biomarkers
                Data availability:
                ScienceOpen disciplines: Pathology
                Keywords: hepatocellular carcinoma, chronic hepatitis, liver cirrhosis, magnetic beads, matri-assisted laser desorption/ionization time-of-flight mass spectrometry, serum biomarkers

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