Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis
Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultras...
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| Veröffentlicht in: | British journal of cancer 2006-01, Vol.94 (2), p.287-292 |
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| creator | Ward, D G Cheng, Y N'kontchou, G Thar, T T Barget, N Wei, W Billingham, L J Martin, A Beaugrand, M Johnson, P J |
| description | Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind’ test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (
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| doi_str_mv | 10.1038/sj.bjc.6602923 |
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P
<0.001) and were identified as
κ
and
λ
immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6602923</identifier><identifier>PMID: 16404431</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amino Acid Sequence ; Base Sequence ; Biological and medical sciences ; Biomarkers, Tumor - blood ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - diagnosis ; Drug Resistance ; Electrophoresis, Polyacrylamide Gel ; Epidemiology ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatitis C ; Hepatitis C - complications ; Humans ; Immunoglobulin G - blood ; Immunoglobulin G - genetics ; Liver cancer ; Liver cirrhosis ; Liver Cirrhosis - etiology ; Liver Neoplasms - blood ; Liver Neoplasms - diagnosis ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Mass spectrometry ; Medical research ; Medical sciences ; Molecular Diagnostics ; Molecular Medicine ; Molecular Sequence Data ; Neural Networks, Computer ; Oncology ; Patients ; Proteins - analysis ; Proteome - analysis ; ROC Curve ; Scientific imaging ; Sensitivity and Specificity ; Serology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Surveillance ; Tumors ; Ultrasonic imaging</subject><ispartof>British journal of cancer, 2006-01, Vol.94 (2), p.287-292</ispartof><rights>The Author(s) 2006</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jan 30, 2006</rights><rights>Copyright © 2006 Cancer Research UK 2006 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-d25c9fb4b1a436c4b57713f95cad5c79dd30055a0f6c6c4291965474e40cd61b3</citedby><cites>FETCH-LOGICAL-c485t-d25c9fb4b1a436c4b57713f95cad5c79dd30055a0f6c6c4291965474e40cd61b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361123/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361123/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17666330$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16404431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ward, D G</creatorcontrib><creatorcontrib>Cheng, Y</creatorcontrib><creatorcontrib>N'kontchou, G</creatorcontrib><creatorcontrib>Thar, T T</creatorcontrib><creatorcontrib>Barget, N</creatorcontrib><creatorcontrib>Wei, W</creatorcontrib><creatorcontrib>Billingham, L J</creatorcontrib><creatorcontrib>Martin, A</creatorcontrib><creatorcontrib>Beaugrand, M</creatorcontrib><creatorcontrib>Johnson, P J</creatorcontrib><title>Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind’ test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (
P
<0.001) and were identified as
κ
and
λ
immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.</description><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - diagnosis</subject><subject>Drug Resistance</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Epidemiology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatitis C</subject><subject>Hepatitis C - complications</subject><subject>Humans</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - genetics</subject><subject>Liver cancer</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - etiology</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - diagnosis</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Mass spectrometry</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Molecular Diagnostics</subject><subject>Molecular Medicine</subject><subject>Molecular Sequence Data</subject><subject>Neural Networks, Computer</subject><subject>Oncology</subject><subject>Patients</subject><subject>Proteins - analysis</subject><subject>Proteome - analysis</subject><subject>ROC Curve</subject><subject>Scientific imaging</subject><subject>Sensitivity and Specificity</subject><subject>Serology</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Surveillance</subject><subject>Tumors</subject><subject>Ultrasonic imaging</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc2r1DAUxYMovvHp1qUEQXedl-9MNoIMfsEDN7oOaZq-prTNmNs-0b_ezExxVHAVwvndc8_lIPScki0lfHcD_bbu_VYpwgzjD9CGSs4qumP6IdoQQnRFDCNX6AlAX76G7PRjdEWVIEJwukE_952b7gLgOOG5CxhCXkZ8yGkOaQzYASQf3Rwa_D3O3Qlpwn0Y0mEM04xTi7twcHPyYRiWwWXsXfZxSqM7Op60OEfA-yqH4eTjY85dgghP0aPWDRCere81-vr-3Zf9x-r284dP-7e3lRc7OVcNk960taipE1x5UUutKW-N9K6RXpum4YRI6UirfJGZoUZJoUUQxDeK1vwavTn7HpZ6DI0vubMb7CHH0eUfNrlo_1am2Nm7dG8ZV5QyXgxerwY5fVsCzHaMcDzYTSEtYDXRlFIiC_jyH7BPS57KcZYxY7QShhRoe4Z8TgA5tL-TUGKPnVrobenUrp2WgRd_5r_ga4kFeLUCDrwb2uwmH-HCaaUU58fNN2cOilRKz5d4_1n9Cx__vUk</recordid><startdate>20060130</startdate><enddate>20060130</enddate><creator>Ward, D G</creator><creator>Cheng, Y</creator><creator>N'kontchou, G</creator><creator>Thar, T T</creator><creator>Barget, N</creator><creator>Wei, W</creator><creator>Billingham, L J</creator><creator>Martin, A</creator><creator>Beaugrand, M</creator><creator>Johnson, P J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20060130</creationdate><title>Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis</title><author>Ward, D G ; Cheng, Y ; N'kontchou, G ; Thar, T T ; Barget, N ; Wei, W ; Billingham, L J ; Martin, A ; Beaugrand, M ; Johnson, P J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-d25c9fb4b1a436c4b57713f95cad5c79dd30055a0f6c6c4291965474e40cd61b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amino Acid Sequence</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - diagnosis</topic><topic>Drug Resistance</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Epidemiology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatitis C</topic><topic>Hepatitis C - complications</topic><topic>Humans</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - genetics</topic><topic>Liver cancer</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - etiology</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - diagnosis</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Mass spectrometry</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Molecular Diagnostics</topic><topic>Molecular Medicine</topic><topic>Molecular Sequence Data</topic><topic>Neural Networks, Computer</topic><topic>Oncology</topic><topic>Patients</topic><topic>Proteins - analysis</topic><topic>Proteome - analysis</topic><topic>ROC Curve</topic><topic>Scientific imaging</topic><topic>Sensitivity and Specificity</topic><topic>Serology</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Surveillance</topic><topic>Tumors</topic><topic>Ultrasonic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ward, D G</creatorcontrib><creatorcontrib>Cheng, Y</creatorcontrib><creatorcontrib>N'kontchou, G</creatorcontrib><creatorcontrib>Thar, T T</creatorcontrib><creatorcontrib>Barget, N</creatorcontrib><creatorcontrib>Wei, W</creatorcontrib><creatorcontrib>Billingham, L J</creatorcontrib><creatorcontrib>Martin, A</creatorcontrib><creatorcontrib>Beaugrand, M</creatorcontrib><creatorcontrib>Johnson, P J</creatorcontrib><collection>Springer Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ward, D G</au><au>Cheng, Y</au><au>N'kontchou, G</au><au>Thar, T T</au><au>Barget, N</au><au>Wei, W</au><au>Billingham, L J</au><au>Martin, A</au><au>Beaugrand, M</au><au>Johnson, P J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2006-01-30</date><risdate>2006</risdate><volume>94</volume><issue>2</issue><spage>287</spage><epage>292</epage><pages>287-292</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Early diagnosis of hepatocellular carcinoma (HCC) is the key to the delivery of effective therapies. The conventional serological diagnostic test, estimation of serum alpha-fetoprotein (AFP) lacks both sensitivity and specificity as a screening tool and improved tests are needed to complement ultrasound scanning, the major modality for surveillance of groups at high risk of HCC. We have analysed the serum proteome of 182 patients with hepatitis C-induced liver cirrhosis (77 with HCC) by surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI). The patients were split into a training set (84 non-HCC, 60 HCC) and a ‘blind’ test set (21 non-HCC, 17 HCC). Neural networks developed on the training set were able to classify the blind test set with 94% sensitivity (95% CI 73–99%) and 86% specificity (95% CI 65–95%). Two of the SELDI peaks (23/23.5 kDa) were elevated by an average of 50% in the serum of HCC patients (
P
<0.001) and were identified as
κ
and
λ
immunoglobulin light chains. This approach may permit identification of several individual proteins, which, in combination, may offer a novel way to diagnose HCC.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16404431</pmid><doi>10.1038/sj.bjc.6602923</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2006-01, Vol.94 (2), p.287-292 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Springer Nature - Connect here FIRST to enable access; PubMed Central; EZB Electronic Journals Library |
| subjects | Amino Acid Sequence Base Sequence Biological and medical sciences Biomarkers, Tumor - blood Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - diagnosis Drug Resistance Electrophoresis, Polyacrylamide Gel Epidemiology Gastroenterology. Liver. Pancreas. Abdomen Hepatitis C Hepatitis C - complications Humans Immunoglobulin G - blood Immunoglobulin G - genetics Liver cancer Liver cirrhosis Liver Cirrhosis - etiology Liver Neoplasms - blood Liver Neoplasms - diagnosis Liver. Biliary tract. Portal circulation. Exocrine pancreas Mass spectrometry Medical research Medical sciences Molecular Diagnostics Molecular Medicine Molecular Sequence Data Neural Networks, Computer Oncology Patients Proteins - analysis Proteome - analysis ROC Curve Scientific imaging Sensitivity and Specificity Serology Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Surveillance Tumors Ultrasonic imaging |
| title | Changes in the serum proteome associated with the development of hepatocellular carcinoma in hepatitis C-related cirrhosis |
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