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Article: Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma

TitleClinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma
Authors
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
Citation
Liver International, 2011, v. 31 n. 10, p. 1494-1504 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/143761
ISSN
2021 Impact Factor: 8.754
2020 SCImago Journal Rankings: 1.873
ISI Accession Number ID
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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTung, EKKen_HK
dc.contributor.authorMak, CKMen_HK
dc.contributor.authorFatima, Sen_HK
dc.contributor.authorLo, RCLen_HK
dc.contributor.authorZhao, Hen_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorDai, Hen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorYuen, MFen_HK
dc.contributor.authorLai, CLen_HK
dc.contributor.authorLi, JJen_HK
dc.contributor.authorLuk, JMCen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2011-12-21T08:54:05Z-
dc.date.available2011-12-21T08:54:05Z-
dc.date.issued2011en_HK
dc.identifier.citationLiver International, 2011, v. 31 n. 10, p. 1494-1504en_HK
dc.identifier.issn1478-3223en_HK
dc.identifier.urihttp://hdl.handle.net/10722/143761-
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.en_HK
dc.languageengen_US
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1en_HK
dc.relation.ispartofLiver Internationalen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.subjectBiomarkeren_HK
dc.subjectDKK1en_HK
dc.subjectHCCen_HK
dc.subjectPrognosisen_HK
dc.subjectWnten_HK
dc.subject.meshCarcinoma, Hepatocellular - blood - metabolismen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshIntercellular Signaling Peptides and Proteins - blood - metabolismen_HK
dc.subject.meshLiver Neoplasms - blood - metabolismen_HK
dc.subject.meshTumor Markers, Biological - blood - metabolismen_HK
dc.titleClinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailLo, RCL: reginalo@pathology.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailYuen, MF: mfyuen@hkucc.hku.hken_HK
dc.identifier.emailLai, CL: hrmelcl@hku.hken_HK
dc.identifier.emailLuk, JMC: jmluk@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityLo, RCL=rp01359en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityYuen, MF=rp00479en_HK
dc.identifier.authorityLai, CL=rp00314en_HK
dc.identifier.authorityLuk, JMC=rp00349en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1478-3231.2011.02597.xen_HK
dc.identifier.pmid21955977-
dc.identifier.scopuseid_2-s2.0-80053997262en_HK
dc.identifier.hkuros197823en_US
dc.identifier.hkuros210703-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80053997262&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume31en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1494en_HK
dc.identifier.epage1504en_HK
dc.identifier.eissn1478-3231-
dc.identifier.isiWOS:000296249800009-
dc.publisher.placeUnited Statesen_HK
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.identifier.scopusauthoridTung, EKK=7003519614en_HK
dc.identifier.scopusauthoridMak, CKM=53983144800en_HK
dc.identifier.scopusauthoridFatima, S=8437472300en_HK
dc.identifier.scopusauthoridLo, RCL=37091058800en_HK
dc.identifier.scopusauthoridZhao, H=53983391800en_HK
dc.identifier.scopusauthoridZhang, C=53983294000en_HK
dc.identifier.scopusauthoridDai, H=7402206916en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridYuen, MF=7102031955en_HK
dc.identifier.scopusauthoridLai, CL=7403086396en_HK
dc.identifier.scopusauthoridLi, JJ=53982819700en_HK
dc.identifier.scopusauthoridLuk, JMC=7006777791en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.issnl1478-3223-

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