Clinicopathological and prognostic significance of serum and tissueDickkopf‐1levels in human hepatocellular carcinoma

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Názov: Clinicopathological and prognostic significance of serum and tissueDickkopf‐1levels in human hepatocellular carcinoma
Autori: Zhang, C, Ng, IOL, Luk, JMC, Li, JJ, Lai, CL, Lo, RCL, Dai, H, Yuen, MF, Poon, RTP, Zhao, H, Fatima, S, Mak, CKM, Tung, EKK
Zdroj: Liver International. 31:1494-1504
Informácie o vydavateľovi: Wiley, 2011.
Rok vydania: 2011
Predmety: Adult, Male, 0301 basic medicine, Carcinoma, Hepatocellular, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, Statistics, Nonparametric, Cell Line, Biological - blood - metabolism, Wnt, 03 medical and health sciences, Cell Movement, Cell Line, Tumor, Biomarkers, Tumor, Humans, Neoplasm Invasiveness, HCC, Tumor Markers, Liver Neoplasms - blood - metabolism, Aged, Oligonucleotide Array Sequence Analysis, 0303 health sciences, Tumor, DKK1, Carcinoma, Liver Neoplasms, Biomarker, Middle Aged, Prognosis, Carcinoma, Hepatocellular - blood - metabolism, Immunohistochemistry, Hepatocellular - blood - metabolism, 3. Good health, Gene Knockdown Techniques, Hong Kong, Intercellular Signaling Peptides and Proteins, Tumor Markers, Biological - blood - metabolism, Female, Intercellular Signaling Peptides and Proteins - blood - metabolism
Popis: Background:Although Dickkopf‐1 (DKK1) is known to be a negative regulator of theWnt/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 transcriptDKK1and its functional roles in human hepatocellular carcinoma (HCC).Methods:We evaluated the expression level ofDKK1 in both tissue and serum samples from patients withHCCusing GeneChip microarray and real‐time‐quantitativePCRand sandwichELISAsystem respectively. The clinicopathological and prognostic significance of serum and tissueDKK1 levels was examined. Functional characterization ofDKK1 with regard to cell migration, invasion and tumour growth was performed.Results:BothDKK1 transcript and serum protein were upregulated in a stepwise manner in humanHCCs. 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 serumDKK1 levels correlated with shorter disease‐free survival (P = 0.046). Knockdown ofDKK1 significantly reduced both migratory and invasive abilities ofHCCcells, whereas overexpression ofDKK1 enhanced the tumour formation efficiency and tumour growthin vivo.Conclusions:Serum and tissueDKK1 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.
Druh dokumentu: Article
Jazyk: English
ISSN: 1478-3231
1478-3223
DOI: 10.1111/j.1478-3231.2011.02597.x
Prístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/21955977
https://core.ac.uk/display/37965730
https://www.ncbi.nlm.nih.gov/pubmed/21955977
http://hub.hku.hk/handle/10722/143761
https://pubmed.ncbi.nlm.nih.gov/21955977/
https://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2011.02597.x
http://hdl.handle.net/10722/143761
Rights: Wiley Online Library User Agreement
Prístupové číslo: edsair.doi.dedup.....7ce87fddac0850b6e74e22b64ab09259
Databáza: OpenAIRE
Popis
Abstrakt:Background:Although Dickkopf‐1 (DKK1) is known to be a negative regulator of theWnt/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 transcriptDKK1and its functional roles in human hepatocellular carcinoma (HCC).Methods:We evaluated the expression level ofDKK1 in both tissue and serum samples from patients withHCCusing GeneChip microarray and real‐time‐quantitativePCRand sandwichELISAsystem respectively. The clinicopathological and prognostic significance of serum and tissueDKK1 levels was examined. Functional characterization ofDKK1 with regard to cell migration, invasion and tumour growth was performed.Results:BothDKK1 transcript and serum protein were upregulated in a stepwise manner in humanHCCs. 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 serumDKK1 levels correlated with shorter disease‐free survival (P = 0.046). Knockdown ofDKK1 significantly reduced both migratory and invasive abilities ofHCCcells, whereas overexpression ofDKK1 enhanced the tumour formation efficiency and tumour growthin vivo.Conclusions:Serum and tissueDKK1 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.
ISSN:14783231
14783223
DOI:10.1111/j.1478-3231.2011.02597.x