Article: Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma
| Title | Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Tung, EKK2 3 Mak, CKM2 Fatima, S2 Lo, RCL2 Zhao, H2 Zhang, C2 4 Dai, H2 4 Poon, RTP2 Yuen, MF1 Lai, CL1 Li, JJ2 Luk, JMC2 Ng, IOL2 | ||||||
| Keywords | Biomarker DKK1 HCC Prognosis Wnt | ||||||
| Issue Date | 2011 | ||||||
| Publisher | Wiley-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?] DOI: http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x | ||||||
| Abstract | Background: 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. | ||||||
| ISSN | 1478-3223 2011 Impact Factor: 3.824 2011 SCImago Journal Rankings: 0.349 | ||||||
| DOI | http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x | ||||||
| ISI Accession Number ID | WOS:000296249800009
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 | References in Scopus | ||||||
| Grants | Molecular pathology of liver cancer - a multidisciplinary study Characterization of regulatory molecules of Wnt/beta-catenin signaling in liver cancer |
| dc.contributor.author | Tung, EKK | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Mak, CKM | ||||||
| dc.contributor.author | Fatima, S | ||||||
| dc.contributor.author | Lo, RCL | ||||||
| dc.contributor.author | Zhao, H | ||||||
| dc.contributor.author | Zhang, C | ||||||
| dc.contributor.author | Dai, H | ||||||
| dc.contributor.author | Poon, RTP | ||||||
| dc.contributor.author | Yuen, MF | ||||||
| dc.contributor.author | Lai, CL | ||||||
| dc.contributor.author | Li, JJ | ||||||
| dc.contributor.author | Luk, JMC | ||||||
| dc.contributor.author | Ng, IOL | ||||||
| dc.date.accessioned | 2011-12-21T08:54:05Z | ||||||
| dc.date.available | 2011-12-21T08:54:05Z | ||||||
| dc.date.issued | 2011 | ||||||
| dc.description.abstract | Background: 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.grant | Molecular pathology of liver cancer - a multidisciplinary study | ||||||
| dc.description.grant | Characterization of regulatory molecules of Wnt/beta-catenin signaling in liver cancer | ||||||
| dc.description.grantcode | 89323 | ||||||
| dc.description.grantcode | 89235 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Liver 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.doi | http://dx.doi.org/10.1111/j.1478-3231.2011.02597.x | ||||||
| dc.identifier.epage | 1504 | ||||||
| dc.identifier.hkuros | 197823 | ||||||
| dc.identifier.hkuros | 210703 | ||||||
| dc.identifier.isi | WOS:000296249800009
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.issn | 1478-3223 2011 Impact Factor: 3.824 2011 SCImago Journal Rankings: 0.349 | ||||||
| dc.identifier.issue | 10 | ||||||
| dc.identifier.pmid | 21955977 | ||||||
| dc.identifier.scopus | eid_2-s2.0-80053997262 | ||||||
| dc.identifier.spage | 1494 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/143761 | ||||||
| dc.identifier.volume | 31 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Wiley-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.place | United States | ||||||
| dc.relation.ispartof | Liver International | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | The definitive version is available at www3.interscience.wiley.com | ||||||
| dc.subject.mesh | Carcinoma, Hepatocellular - blood - metabolism | ||||||
| dc.subject.mesh | Cell Line, Tumor | ||||||
| dc.subject.mesh | Intercellular Signaling Peptides and Proteins - blood - metabolism | ||||||
| dc.subject.mesh | Liver Neoplasms - blood - metabolism | ||||||
| dc.subject.mesh | Tumor Markers, Biological - blood - metabolism | ||||||
| dc.subject | Biomarker | ||||||
| dc.subject | DKK1 | ||||||
| dc.subject | HCC | ||||||
| dc.subject | Prognosis | ||||||
| dc.subject | Wnt | ||||||
| dc.title | Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma | ||||||
| dc.type | Article |
Author Affiliations
- Merck Research Laboratories
- The University of Hong Kong
- National University of Singapore
- Shanghai Jiao Tong University School of Medicine