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Article: Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma
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TitleClinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma
 
AuthorsTung, EKK1 3
Mak, CKM1
Fatima, S1
Lo, RCL1
Zhao, H1
Zhang, C1 4
Dai, H1 4
Poon, RTP1
Yuen, MF2
Lai, CL2
Li, JJ1
Luk, JMC1
Ng, IOL1
 
KeywordsBiomarker
DKK1
HCC
Prognosis
Wnt
 
Issue Date2011
 
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
 
CitationLiver International, 2011, v. 31 n. 10, p. 1494-1504 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x
 
AbstractBackground: Although Dickkopf-1 (DKK1) is known to be a negative regulator of the Wnt/β-catenin pathway, it has been recently found to be upregulated in cancers. Aims:: We investigated the clinical and prognostic significance of both serum and transcript DKK1 and its functional roles in human hepatocellular carcinoma (HCC). Methods:: We evaluated the expression level of DKK1 in both tissue and serum samples from patients with HCC using GeneChip microarray and real-time-quantitative PCR and sandwich ELISA system respectively. The clinicopathological and prognostic significance of serum and tissue DKK1 levels was examined. Functional characterization of DKK1 with regard to cell migration, invasion and tumour growth was performed. Results:: Both DKK1 transcript and serum protein were upregulated in a stepwise manner in human HCCs. Its transcript levels were associated with more aggressive tumour behaviour, in terms of venous invasion (P = 0.003), advanced tumour stage (P = 0.003). DKK1 transcript correlated with shorter overall (P = 0.006) and disease-free survival (P = 0.012), and higher serum DKK1 levels correlated with shorter disease-free survival (P = 0.046). Knockdown of DKK1 significantly reduced both migratory and invasive abilities of HCC cells, whereas overexpression of DKK1 enhanced the tumour formation efficiency and tumour growth in vivo. Conclusions:: Serum and tissue DKK1 levels increased in a stepwise manner in multistep hepatocarcinogenesis and had prognostic significance. DKK1 plays a functional role in cell migration, invasion and tumour growth. © 2011 John Wiley & Sons A/S.
 
ISSN1478-3223
2013 Impact Factor: 4.412
 
DOIhttp://dx.doi.org/10.1111/j.1478-3231.2011.02597.x
 
ISI Accession Number IDWOS:000296249800009
Funding AgencyGrant Number
NSFC/RGCN_HKU 716/06
RGCHKU 1/06C
HKU 7/CRG/09
Funding Information:

The study was supported in part by a grant from the NSFC/RGC Joint Research Scheme (N_HKU 716/06) and RGC Collaborative Research Grant (HKU 1/06C and HKU 7/CRG/09). I. O. L. Ng is Loke Yew Professor in Pathology.

 
ReferencesReferences in Scopus
 
GrantsMolecular pathology of liver cancer - a multidisciplinary study
Characterization of regulatory molecules of Wnt/beta-catenin signaling in liver cancer
 
DC FieldValue
dc.contributor.authorTung, EKK
 
dc.contributor.authorMak, CKM
 
dc.contributor.authorFatima, S
 
dc.contributor.authorLo, RCL
 
dc.contributor.authorZhao, H
 
dc.contributor.authorZhang, C
 
dc.contributor.authorDai, H
 
dc.contributor.authorPoon, RTP
 
dc.contributor.authorYuen, MF
 
dc.contributor.authorLai, CL
 
dc.contributor.authorLi, JJ
 
dc.contributor.authorLuk, JMC
 
dc.contributor.authorNg, IOL
 
dc.date.accessioned2011-12-21T08:54:05Z
 
dc.date.available2011-12-21T08:54:05Z
 
dc.date.issued2011
 
dc.description.abstractBackground: Although Dickkopf-1 (DKK1) is known to be a negative regulator of the Wnt/β-catenin pathway, it has been recently found to be upregulated in cancers. Aims:: We investigated the clinical and prognostic significance of both serum and transcript DKK1 and its functional roles in human hepatocellular carcinoma (HCC). Methods:: We evaluated the expression level of DKK1 in both tissue and serum samples from patients with HCC using GeneChip microarray and real-time-quantitative PCR and sandwich ELISA system respectively. The clinicopathological and prognostic significance of serum and tissue DKK1 levels was examined. Functional characterization of DKK1 with regard to cell migration, invasion and tumour growth was performed. Results:: Both DKK1 transcript and serum protein were upregulated in a stepwise manner in human HCCs. Its transcript levels were associated with more aggressive tumour behaviour, in terms of venous invasion (P = 0.003), advanced tumour stage (P = 0.003). DKK1 transcript correlated with shorter overall (P = 0.006) and disease-free survival (P = 0.012), and higher serum DKK1 levels correlated with shorter disease-free survival (P = 0.046). Knockdown of DKK1 significantly reduced both migratory and invasive abilities of HCC cells, whereas overexpression of DKK1 enhanced the tumour formation efficiency and tumour growth in vivo. Conclusions:: Serum and tissue DKK1 levels increased in a stepwise manner in multistep hepatocarcinogenesis and had prognostic significance. DKK1 plays a functional role in cell migration, invasion and tumour growth. © 2011 John Wiley & Sons A/S.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationLiver International, 2011, v. 31 n. 10, p. 1494-1504 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1478-3231.2011.02597.x
 
dc.identifier.eissn1478-3231
 
dc.identifier.epage1504
 
dc.identifier.hkuros197823
 
dc.identifier.hkuros210703
 
dc.identifier.isiWOS:000296249800009
Funding AgencyGrant Number
NSFC/RGCN_HKU 716/06
RGCHKU 1/06C
HKU 7/CRG/09
Funding Information:

The study was supported in part by a grant from the NSFC/RGC Joint Research Scheme (N_HKU 716/06) and RGC Collaborative Research Grant (HKU 1/06C and HKU 7/CRG/09). I. O. L. Ng is Loke Yew Professor in Pathology.

 
dc.identifier.issn1478-3223
2013 Impact Factor: 4.412
 
dc.identifier.issue10
 
dc.identifier.pmid21955977
 
dc.identifier.scopuseid_2-s2.0-80053997262
 
dc.identifier.spage1494
 
dc.identifier.urihttp://hdl.handle.net/10722/143761
 
dc.identifier.volume31
 
dc.languageeng
 
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
 
dc.publisher.placeUnited States
 
dc.relation.ispartofLiver International
 
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study
 
dc.relation.projectCharacterization of regulatory molecules of Wnt/beta-catenin signaling in liver cancer
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe definitive version is available at www3.interscience.wiley.com
 
dc.subject.meshCarcinoma, Hepatocellular - blood - metabolism
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshIntercellular Signaling Peptides and Proteins - blood - metabolism
 
dc.subject.meshLiver Neoplasms - blood - metabolism
 
dc.subject.meshTumor Markers, Biological - blood - metabolism
 
dc.subjectBiomarker
 
dc.subjectDKK1
 
dc.subjectHCC
 
dc.subjectPrognosis
 
dc.subjectWnt
 
dc.titleClinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma
 
dc.typeArticle
 
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<contributor.author>Fatima, S</contributor.author>
<contributor.author>Lo, RCL</contributor.author>
<contributor.author>Zhao, H</contributor.author>
<contributor.author>Zhang, C</contributor.author>
<contributor.author>Dai, H</contributor.author>
<contributor.author>Poon, RTP</contributor.author>
<contributor.author>Yuen, MF</contributor.author>
<contributor.author>Lai, CL</contributor.author>
<contributor.author>Li, JJ</contributor.author>
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<description.abstract>Background: Although Dickkopf-1 (DKK1) is known to be a negative regulator of the Wnt/&#946;-catenin pathway, it has been recently found to be upregulated in cancers. Aims:: We investigated the clinical and prognostic significance of both serum and transcript DKK1 and its functional roles in human hepatocellular carcinoma (HCC). Methods:: We evaluated the expression level of DKK1 in both tissue and serum samples from patients with HCC using GeneChip microarray and real-time-quantitative PCR and sandwich ELISA system respectively. The clinicopathological and prognostic significance of serum and tissue DKK1 levels was examined. Functional characterization of DKK1 with regard to cell migration, invasion and tumour growth was performed. Results:: Both DKK1 transcript and serum protein were upregulated in a stepwise manner in human HCCs. Its transcript levels were associated with more aggressive tumour behaviour, in terms of venous invasion (P = 0.003), advanced tumour stage (P = 0.003). DKK1 transcript correlated with shorter overall (P = 0.006) and disease-free survival (P = 0.012), and higher serum DKK1 levels correlated with shorter disease-free survival (P = 0.046). Knockdown of DKK1 significantly reduced both migratory and invasive abilities of HCC cells, whereas overexpression of DKK1 enhanced the tumour formation efficiency and tumour growth in vivo. Conclusions:: Serum and tissue DKK1 levels increased in a stepwise manner in multistep hepatocarcinogenesis and had prognostic significance. DKK1 plays a functional role in cell migration, invasion and tumour growth. &#169; 2011 John Wiley &amp; Sons A/S.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Merck Research Laboratories
  3. National University of Singapore
  4. Shanghai Jiao Tong University School of Medicine