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Article: Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma

TitleProteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma
Authors
KeywordsDiagnosis and prognosis
Hepatocellular carcinoma
Proteomics
Tumor markers
Issue Date2009
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs
Citation
Journal Of Proteome Research, 2009, v. 8 n. 3, p. 1293-1303 How to Cite?
AbstractHepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak's score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression. © 2009 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/69559
ISSN
2015 Impact Factor: 4.173
2015 SCImago Journal Rankings: 1.962
ISI Accession Number ID
Funding AgencyGrant Number
Council of Hong KongN_HKU 718/03
Innovation and Technology FundITS/120/07
Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery
Funding Information:

The authors gratefully acknowledge the clinical supports and technical assistance provided by Wan-Ching Yu, Pauline Leung, and Stanley Lam of the Department of Surgery of The University of Hong Kong; insightful advice and comments by Professor S. T. Fan (Queen Mary Hospital, HK); expert opinion and advice on CART algorithm and proteomic data analysis by Dr. Brian Lam (Deptartment of Pharmacology, University of Cambridge, U.K.) and Dr. Xin Yi (Fred Hutchinson Cancer Research Center, Seattle, WA). The work was supported by the Research Grants Council of Hong Kong (N_HKU 718/03), Innovation and Technology Fund (ITS/120/07) and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLee, NPen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorLin, MCen_HK
dc.contributor.authorTsang, FHen_HK
dc.contributor.authorYeung, Cen_HK
dc.contributor.authorPoon, RTen_HK
dc.contributor.authorPeng, Jen_HK
dc.contributor.authorLeng, Xen_HK
dc.contributor.authorBeretta, Len_HK
dc.contributor.authorSun, Sen_HK
dc.contributor.authorDay, PJen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2010-09-06T06:14:47Z-
dc.date.available2010-09-06T06:14:47Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Proteome Research, 2009, v. 8 n. 3, p. 1293-1303en_HK
dc.identifier.issn1535-3893en_HK
dc.identifier.urihttp://hdl.handle.net/10722/69559-
dc.description.abstractHepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin I) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak's score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression. © 2009 American Chemical Society.en_HK
dc.languageengen_HK
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobsen_HK
dc.relation.ispartofJournal of Proteome Researchen_HK
dc.subjectDiagnosis and prognosisen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectProteomicsen_HK
dc.subjectTumor markersen_HK
dc.subject.meshCarcinoma, Hepatocellular - complications - metabolism-
dc.subject.meshLiver Neoplasms - complications - metabolism-
dc.subject.meshProteome - metabolism-
dc.subject.meshSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization-
dc.subject.meshTumor Markers, Biological - metabolism-
dc.titleProteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1535-3893&volume=8&issue=3&spage=1293&epage=1303&date=2009&atitle=Proteomic+expression+signature+distinguishes+cancerous+and+nonmalignant+tissues+in+hepatocellular+carcinomaen_HK
dc.identifier.emailLee, NP: nikkilee@hku.hken_HK
dc.identifier.emailLin, MC: mcllin@hkucc.hku.hken_HK
dc.identifier.emailPoon, RT: poontp@hkucc.hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLee, NP=rp00263en_HK
dc.identifier.authorityLin, MC=rp00746en_HK
dc.identifier.authorityPoon, RT=rp00446en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/pr800637zen_HK
dc.identifier.pmid19161326-
dc.identifier.scopuseid_2-s2.0-65249107192en_HK
dc.identifier.hkuros170085en_HK
dc.identifier.hkuros162687-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65249107192&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume8en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1293en_HK
dc.identifier.epage1303en_HK
dc.identifier.isiWOS:000264035000019-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectDifferential proteomic analysis of biomarkers for primary and recurrent hepatocellular carcinoma-
dc.relation.projectLiver cancer biomarker test: diagnostic use of CDH17 monoclonal antibodies-
dc.identifier.scopusauthoridLee, NP=7402722690en_HK
dc.identifier.scopusauthoridChen, L=7409441990en_HK
dc.identifier.scopusauthoridLin, MC=7404816359en_HK
dc.identifier.scopusauthoridTsang, FH=36895782100en_HK
dc.identifier.scopusauthoridYeung, C=26531966700en_HK
dc.identifier.scopusauthoridPoon, RT=7103097223en_HK
dc.identifier.scopusauthoridPeng, J=7401958598en_HK
dc.identifier.scopusauthoridLeng, X=7102492468en_HK
dc.identifier.scopusauthoridBeretta, L=7005190156en_HK
dc.identifier.scopusauthoridSun, S=21740136100en_HK
dc.identifier.scopusauthoridDay, PJ=7202148832en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK

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