Article: Proteomics of hepatocellular carcinoma: Serum vimentin as a surrogate marker for small tumors (≤2 cm)

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
TitleProteomics of hepatocellular carcinoma: Serum vimentin as a surrogate marker for small tumors (≤2 cm)
AuthorsSun, S2
Poon, RTP2
Lee, NP2
Yeung, C2
Chan, KL2
Ng, IOL2
Day, PJR1
Luk, JM2 3
KeywordsAFP
Biomarker
Cancer screening
HCC
Tumor detection
Tumor size
Issue Date2010
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs
CitationJournal Of Proteome Research, 2010, v. 9 n. 4, p. 1923-1930 [How to Cite?]
DOI: http://dx.doi.org/10.1021/pr901085z
AbstractSmall hepatocellular carcinomas (HCCs) can be effectively cured by surgery with good clinical outcomes. However, the conventional AFP marker is ineffective in detecting small tumors. Here we employed a proteomic profiling approach to identify a candidate marker for HCC (≤2 cm) in tumor tissues and then evaluate its clinical feasibility in patients? sera. The study was divided into 2 phases. (i) Biomarker discovery: we collected 76 frozen liver tissues (40 HCC and 36 controls) for proteomics profiling. Candidate protein markers were identified by MALDI-TOF/TOF and confirmed by immunoblot and qPCR. (ii) Clinical evaluation: Selected biomarker was tested by ELISA for sensitivity and specificity using serum samples from a separate cohort of 152 subjects (88 HCC and 64 controls). Vimentin was found significantly overexpressed in HCC, in particular the small-size subgroup (≤2 cm) with p < 0.01. When tested in the serum samples, vimentin level was significantly higher in small tumors than the non-neoplastic controls (AUC = 0.69 and p < 0.01). Further analysis suggested that elevated circulating vimentin level could detect small HCC at 40.91% sensitivity and 87.50% specificity. Moreover, vimentin was found to be superior to serum AFP assayed at different cut-offs in detecting small tumors. When combined with AFP, the detection sensitivity and specificity could be further enhanced to 58.77 and 98.15%, respectively. In conclusion, serum vimentin is a potential surrogate marker, either alone or in combination with AFP, for detection of small HCCs. © 2010 American Chemical Society.
ISSN1535-3893
2011 Impact Factor: 5.113
2011 SCImago Journal Rankings: 0.642
DOIhttp://dx.doi.org/10.1021/pr901085z
ISI Accession Number IDWOS:000276215700028
Funding AgencyGrant Number
Research Grants Council of Hong Kong771607M
National Medical Research Council
Funding Information:

The work was supported by grants from the Research Grants Council of Hong Kong (771607M) and National Medical Research Council to J.M.L. We also thank for the generous donation from the Sun Chien Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery. We sincerely acknowledge Dr. W. C. Yu for giving clinical assistance in specimen collection and preparation. We also thank Dr. Wilson Y.P. Ching in Department of Anatomy, The University of Hong Kong for providing the monoclonal vimentin antibody in our preliminary studies. Irene Ng is Loke Yew Professor of Pathology.

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorSun, S
dc.contributor.authorPoon, RTP
dc.contributor.authorLee, NP
dc.contributor.authorYeung, C
dc.contributor.authorChan, KL
dc.contributor.authorNg, IOL
dc.contributor.authorDay, PJR
dc.contributor.authorLuk, JM
dc.date.accessioned2010-09-06T09:43:54Z
dc.date.available2010-09-06T09:43:54Z
dc.date.issued2010
dc.description.abstractSmall hepatocellular carcinomas (HCCs) can be effectively cured by surgery with good clinical outcomes. However, the conventional AFP marker is ineffective in detecting small tumors. Here we employed a proteomic profiling approach to identify a candidate marker for HCC (≤2 cm) in tumor tissues and then evaluate its clinical feasibility in patients? sera. The study was divided into 2 phases. (i) Biomarker discovery: we collected 76 frozen liver tissues (40 HCC and 36 controls) for proteomics profiling. Candidate protein markers were identified by MALDI-TOF/TOF and confirmed by immunoblot and qPCR. (ii) Clinical evaluation: Selected biomarker was tested by ELISA for sensitivity and specificity using serum samples from a separate cohort of 152 subjects (88 HCC and 64 controls). Vimentin was found significantly overexpressed in HCC, in particular the small-size subgroup (≤2 cm) with p < 0.01. When tested in the serum samples, vimentin level was significantly higher in small tumors than the non-neoplastic controls (AUC = 0.69 and p < 0.01). Further analysis suggested that elevated circulating vimentin level could detect small HCC at 40.91% sensitivity and 87.50% specificity. Moreover, vimentin was found to be superior to serum AFP assayed at different cut-offs in detecting small tumors. When combined with AFP, the detection sensitivity and specificity could be further enhanced to 58.77 and 98.15%, respectively. In conclusion, serum vimentin is a potential surrogate marker, either alone or in combination with AFP, for detection of small HCCs. © 2010 American Chemical Society.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Proteome Research, 2010, v. 9 n. 4, p. 1923-1930 [How to Cite?]
DOI: http://dx.doi.org/10.1021/pr901085z
dc.identifier.doihttp://dx.doi.org/10.1021/pr901085z
dc.identifier.epage1930
dc.identifier.hkuros169635
dc.identifier.isiWOS:000276215700028
Funding AgencyGrant Number
Research Grants Council of Hong Kong771607M
National Medical Research Council
Funding Information:

The work was supported by grants from the Research Grants Council of Hong Kong (771607M) and National Medical Research Council to J.M.L. We also thank for the generous donation from the Sun Chien Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery. We sincerely acknowledge Dr. W. C. Yu for giving clinical assistance in specimen collection and preparation. We also thank Dr. Wilson Y.P. Ching in Department of Anatomy, The University of Hong Kong for providing the monoclonal vimentin antibody in our preliminary studies. Irene Ng is Loke Yew Professor of Pathology.

dc.identifier.issn1535-3893
2011 Impact Factor: 5.113
2011 SCImago Journal Rankings: 0.642
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid20121168
dc.identifier.scopuseid_2-s2.0-77950647292
dc.identifier.spage1923
dc.identifier.urihttp://hdl.handle.net/10722/88478
dc.identifier.volume9
dc.languageeng
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jprobs
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Proteome Research
dc.relation.referencesReferences in Scopus
dc.subject.meshCarcinoma, Hepatocellular - blood - diagnosis - pathology
dc.subject.meshLiver Neoplasms - blood - diagnosis - pathology
dc.subject.meshProteomics - methods
dc.subject.meshTumor Markers, Biological - blood
dc.subject.meshVimentin - blood
dc.subjectAFP
dc.subjectBiomarker
dc.subjectCancer screening
dc.subjectHCC
dc.subjectTumor detection
dc.subjectTumor size
dc.titleProteomics of hepatocellular carcinoma: Serum vimentin as a surrogate marker for small tumors (≤2 cm)
dc.typeArticle
Author Affiliations
  1. University of Manchester
  2. The University of Hong Kong
  3. National University of Singapore