Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors

BACKGROUND Differentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to dist...

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Veröffentlicht in:Medical science monitor 2017-04, Vol.23, p.1636-1644
Hauptverfasser: Li, Bo, Li, Boan, Guo, Tongsheng, Sun, Zhiqiang, Li, Xiaohan, Li, Xiaoxi, Wang, Han, Chen, Weijiao, Chen, Peng, Qiao, Mengran, Xia, Lifang, Mao, Yuanli
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container_title Medical science monitor
container_volume 23
creator Li, Bo
Li, Boan
Guo, Tongsheng
Sun, Zhiqiang
Li, Xiaohan
Li, Xiaoxi
Wang, Han
Chen, Weijiao
Chen, Peng
Qiao, Mengran
Xia, Lifang
Mao, Yuanli
description BACKGROUND Differentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry. MATERIAL AND METHODS In our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system. RESULTS A total of 27 discriminant peaks (p
doi_str_mv 10.12659/msm.901064
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In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry. MATERIAL AND METHODS In our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system. RESULTS A total of 27 discriminant peaks (p&lt;0.05) in mass spectra of serum samples were found by ClinPro Tools software. Recognition capabilities of the established models were 100% (GA), 89.38% (SNN), and 80.84% (QC); cross-validation rates were 81.67% (GA), 81.11% (SNN), and 86.11% (QC). The accuracy rates of the blinded validation test were 78% (GA), 84% (SNN), and 84% (QC). From the 27 discriminatory peptide peaks analyzed, 3 peaks of m/z 2860.34, 2881.54, and 3155.67 were identified as a fragment of fibrinogen alpha chain, fibrinogen beta chain, and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), respectively. CONCLUSIONS Our results demonstrated that MS technique can be helpful in differentiation of benign and malignant liver tumors. Fibrinogen and ITIH4 might be used as biomarkers for the diagnosis of malignant liver tumors.</description><identifier>ISSN: 1643-3750</identifier><identifier>ISSN: 1234-1010</identifier><identifier>EISSN: 1643-3750</identifier><identifier>DOI: 10.12659/msm.901064</identifier><identifier>PMID: 28376075</identifier><language>eng</language><publisher>United States: International Scientific Literature, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - blood ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - diagnostic imaging ; Carcinoma, Hepatocellular - pathology ; Female ; Humans ; Liver Neoplasms - blood ; Liver Neoplasms - diagnosis ; Liver Neoplasms - diagnostic imaging ; Liver Neoplasms - pathology ; Male ; Middle Aged ; Molecular Biology ; Peptides - blood ; Proteomics - methods ; Reproducibility of Results ; Sequence Analysis, Protein - methods ; Software ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><ispartof>Medical science monitor, 2017-04, Vol.23, p.1636-1644</ispartof><rights>Med Sci Monit, 2017 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-831a45b5a00b2218df47b8bb7d7ac7ab4cc47ad8cbcfef37459b2ec6770b50a43</citedby><cites>FETCH-LOGICAL-c489t-831a45b5a00b2218df47b8bb7d7ac7ab4cc47ad8cbcfef37459b2ec6770b50a43</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/PMC5388305/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5388305/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28376075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Li, Boan</creatorcontrib><creatorcontrib>Guo, Tongsheng</creatorcontrib><creatorcontrib>Sun, Zhiqiang</creatorcontrib><creatorcontrib>Li, Xiaohan</creatorcontrib><creatorcontrib>Li, Xiaoxi</creatorcontrib><creatorcontrib>Wang, Han</creatorcontrib><creatorcontrib>Chen, Weijiao</creatorcontrib><creatorcontrib>Chen, Peng</creatorcontrib><creatorcontrib>Qiao, Mengran</creatorcontrib><creatorcontrib>Xia, Lifang</creatorcontrib><creatorcontrib>Mao, Yuanli</creatorcontrib><title>Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors</title><title>Medical science monitor</title><addtitle>Med Sci Monit</addtitle><description>BACKGROUND Differentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry. MATERIAL AND METHODS In our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system. RESULTS A total of 27 discriminant peaks (p&lt;0.05) in mass spectra of serum samples were found by ClinPro Tools software. Recognition capabilities of the established models were 100% (GA), 89.38% (SNN), and 80.84% (QC); cross-validation rates were 81.67% (GA), 81.11% (SNN), and 86.11% (QC). The accuracy rates of the blinded validation test were 78% (GA), 84% (SNN), and 84% (QC). From the 27 discriminatory peptide peaks analyzed, 3 peaks of m/z 2860.34, 2881.54, and 3155.67 were identified as a fragment of fibrinogen alpha chain, fibrinogen beta chain, and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), respectively. CONCLUSIONS Our results demonstrated that MS technique can be helpful in differentiation of benign and malignant liver tumors. Fibrinogen and ITIH4 might be used as biomarkers for the diagnosis of malignant liver tumors.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - blood</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - diagnostic imaging</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - diagnosis</subject><subject>Liver Neoplasms - diagnostic imaging</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular Biology</subject><subject>Peptides - blood</subject><subject>Proteomics - methods</subject><subject>Reproducibility of Results</subject><subject>Sequence Analysis, Protein - methods</subject><subject>Software</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</subject><issn>1643-3750</issn><issn>1234-1010</issn><issn>1643-3750</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUUlLAzEYDaLYupy8S46CtCaTZJJehFpXaPHgcg1JJtNGZpIxmSn47x2tFj19D763wQPgBKMxznI2uahTPZ4gjHK6A4Y4p2REOEO7f_AAHKT0hlAmcsT2wSAThOeIsyHQ06apnFGtCx6-qqqzMJRwoVKCT401bQy1beMHdB62KwuvXVnaaH3rNoqee2W9W3qofNHLqh4q38K5W9sIn7s6xHQE9kpVJXv8cw_By-3N8-x-NH-8e5hN5yNDxaQdCYIVZZophHSWYVGUlGuhNS-4MlxpagzlqhBGm9KWhFM20Zk1OedIM6QoOQSXG9-m07UtTN8yqko20dUqfsignPz_8W4ll2EtGRGCINYbnP0YxPDe2dTK2iVjq0p5G7oksRCU5pjjr6zzDdXEkFK05TYGI_m9ilw8LeRmlZ59-rfZlvs7A_kE4KWKqA</recordid><startdate>20170404</startdate><enddate>20170404</enddate><creator>Li, Bo</creator><creator>Li, Boan</creator><creator>Guo, Tongsheng</creator><creator>Sun, Zhiqiang</creator><creator>Li, Xiaohan</creator><creator>Li, Xiaoxi</creator><creator>Wang, Han</creator><creator>Chen, Weijiao</creator><creator>Chen, Peng</creator><creator>Qiao, Mengran</creator><creator>Xia, Lifang</creator><creator>Mao, Yuanli</creator><general>International Scientific Literature, Inc</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170404</creationdate><title>Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors</title><author>Li, Bo ; Li, Boan ; Guo, Tongsheng ; Sun, Zhiqiang ; Li, Xiaohan ; Li, Xiaoxi ; Wang, Han ; Chen, Weijiao ; Chen, Peng ; Qiao, Mengran ; Xia, Lifang ; Mao, Yuanli</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-831a45b5a00b2218df47b8bb7d7ac7ab4cc47ad8cbcfef37459b2ec6770b50a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - blood</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - diagnostic imaging</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - diagnosis</topic><topic>Liver Neoplasms - diagnostic imaging</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular Biology</topic><topic>Peptides - blood</topic><topic>Proteomics - methods</topic><topic>Reproducibility of Results</topic><topic>Sequence Analysis, Protein - methods</topic><topic>Software</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods</topic><toplevel>online_resources</toplevel><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Li, Boan</creatorcontrib><creatorcontrib>Guo, Tongsheng</creatorcontrib><creatorcontrib>Sun, Zhiqiang</creatorcontrib><creatorcontrib>Li, Xiaohan</creatorcontrib><creatorcontrib>Li, Xiaoxi</creatorcontrib><creatorcontrib>Wang, Han</creatorcontrib><creatorcontrib>Chen, Weijiao</creatorcontrib><creatorcontrib>Chen, Peng</creatorcontrib><creatorcontrib>Qiao, Mengran</creatorcontrib><creatorcontrib>Xia, Lifang</creatorcontrib><creatorcontrib>Mao, Yuanli</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medical science monitor</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Bo</au><au>Li, Boan</au><au>Guo, Tongsheng</au><au>Sun, Zhiqiang</au><au>Li, Xiaohan</au><au>Li, Xiaoxi</au><au>Wang, Han</au><au>Chen, Weijiao</au><au>Chen, Peng</au><au>Qiao, Mengran</au><au>Xia, Lifang</au><au>Mao, Yuanli</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors</atitle><jtitle>Medical science monitor</jtitle><addtitle>Med Sci Monit</addtitle><date>2017-04-04</date><risdate>2017</risdate><volume>23</volume><spage>1636</spage><epage>1644</epage><pages>1636-1644</pages><issn>1643-3750</issn><issn>1234-1010</issn><eissn>1643-3750</eissn><abstract>BACKGROUND Differentiation of malignant from benign liver tumors remains a challenging problem. In recent years, mass spectrometry (MS) technique has emerged as a promising strategy to diagnose a wide range of malignant tumors. The purpose of this study was to establish classification models to distinguish benign and malignant liver tumors and identify the liver cancer-specific peptides by mass spectrometry. MATERIAL AND METHODS In our study, serum samples from 43 patients with malignant liver tumors and 52 patients with benign liver tumors were treated with weak cation-exchange chromatography Magnetic Beads (MB-WCX) kits and analyzed by the Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry (MALDI-TOF-MS). Then we established genetic algorithm (GA), supervised neural networks (SNN), and quick classifier (QC) models to distinguish malignant from benign liver tumors. To confirm the clinical applicability of the established models, the blinded validation test was performed in 50 clinical serum samples. Discriminatory peaks associated with malignant liver tumors were subsequently identified by a qTOF Synapt G2-S system. RESULTS A total of 27 discriminant peaks (p&lt;0.05) in mass spectra of serum samples were found by ClinPro Tools software. Recognition capabilities of the established models were 100% (GA), 89.38% (SNN), and 80.84% (QC); cross-validation rates were 81.67% (GA), 81.11% (SNN), and 86.11% (QC). The accuracy rates of the blinded validation test were 78% (GA), 84% (SNN), and 84% (QC). From the 27 discriminatory peptide peaks analyzed, 3 peaks of m/z 2860.34, 2881.54, and 3155.67 were identified as a fragment of fibrinogen alpha chain, fibrinogen beta chain, and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), respectively. CONCLUSIONS Our results demonstrated that MS technique can be helpful in differentiation of benign and malignant liver tumors. Fibrinogen and ITIH4 might be used as biomarkers for the diagnosis of malignant liver tumors.</abstract><cop>United States</cop><pub>International Scientific Literature, Inc</pub><pmid>28376075</pmid><doi>10.12659/msm.901064</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Aged, 80 and over
Biomarkers, Tumor - blood
Carcinoma, Hepatocellular - blood
Carcinoma, Hepatocellular - diagnostic imaging
Carcinoma, Hepatocellular - pathology
Female
Humans
Liver Neoplasms - blood
Liver Neoplasms - diagnosis
Liver Neoplasms - diagnostic imaging
Liver Neoplasms - pathology
Male
Middle Aged
Molecular Biology
Peptides - blood
Proteomics - methods
Reproducibility of Results
Sequence Analysis, Protein - methods
Software
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods
title Application Value of Mass Spectrometry in the Differentiation of Benign and Malignant Liver Tumors
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