Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma
Background and aims The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection. Methods One-hundred and four cases of matched fresh tissue specimens...
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| Veröffentlicht in: | The International journal of biological markers 2013-07, Vol.28 (3), p.286-297 |
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| container_title | The International journal of biological markers |
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| creator | Yang, Hao Chen, Guo-Dong Fang, Feng Liu, Zhen Hiu Yan Lau, Stephanie Zhang, Jin-Fan Lau, Wan Yee Yang, Lian-Yue |
| description | Background and aims
The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection.
Methods
One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured.
Results
The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p |
| doi_str_mv | 10.5301/JBM.5000015 |
| format | Article |
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The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection.
Methods
One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured.
Results
The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival.
Conclusions
Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.</description><identifier>ISSN: 0393-6155</identifier><identifier>EISSN: 1724-6008</identifier><identifier>DOI: 10.5301/JBM.5000015</identifier><identifier>PMID: 23568769</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Aged ; alpha-Fetoproteins - metabolism ; Biomarkers, Tumor - blood ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - pathology ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins - blood ; Liver Neoplasms - blood ; Liver Neoplasms - pathology ; Male ; Middle Aged ; Prognosis ; Survival Analysis</subject><ispartof>The International journal of biological markers, 2013-07, Vol.28 (3), p.286-297</ispartof><rights>2013 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-d9429e711757b6c5224c53cc2a1f154a18c199710846937ac2b6acf8cd6f88f43</citedby><cites>FETCH-LOGICAL-c467t-d9429e711757b6c5224c53cc2a1f154a18c199710846937ac2b6acf8cd6f88f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.5301/JBM.5000015$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.5301/JBM.5000015$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21966,27853,27924,27925,44945,45333</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.5301/JBM.5000015?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23568769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yang, Hao</creatorcontrib><creatorcontrib>Chen, Guo-Dong</creatorcontrib><creatorcontrib>Fang, Feng</creatorcontrib><creatorcontrib>Liu, Zhen</creatorcontrib><creatorcontrib>Hiu Yan Lau, Stephanie</creatorcontrib><creatorcontrib>Zhang, Jin-Fan</creatorcontrib><creatorcontrib>Lau, Wan Yee</creatorcontrib><creatorcontrib>Yang, Lian-Yue</creatorcontrib><title>Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma</title><title>The International journal of biological markers</title><addtitle>Int J Biol Markers</addtitle><description>Background and aims
The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection.
Methods
One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured.
Results
The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival.
Conclusions
Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.</description><subject>Aged</subject><subject>alpha-Fetoproteins - metabolism</subject><subject>Biomarkers, Tumor - blood</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Intercellular Signaling Peptides and Proteins - blood</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Survival Analysis</subject><issn>0393-6155</issn><issn>1724-6008</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkD1PwzAQhi0EouVjYkcekVCKz4nthK20hYJagQQsLNHVdaq0SVzsZOi_J1VbWLjldNKj9-4eQq6A9UTI4O7lYdoTrC0QR6QLikeBZCw-Jl0WJmEgQYgOOfN-yRgHpuQp6fBQyFjJpEu-hrlerew6C-Ce9j1FOsxxUVlf55piNadvzh7Gd-Oakk7RrYyjmXV0hK7Y0LFZY221KYqmQEcH6HRe2RIvyEmGhTeX-35OPh9HH4NxMHl9eh70J4GOpKqDeRLxxCgAJdRMasF5pEWoNUfIQEQIsYYkUcDiSCahQs1nEnUW67nM4jiLwnNys8tdO_vdGF-nZe6352BlbONTUIyzOAkFtOjtDtXOeu9Mlq5dXqLbpMDSrcy0lZnuZbb09T64mZVm_sse7P1t9rgw6dI2rmof_TfrB6jiecs</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Yang, Hao</creator><creator>Chen, Guo-Dong</creator><creator>Fang, Feng</creator><creator>Liu, Zhen</creator><creator>Hiu Yan Lau, Stephanie</creator><creator>Zhang, Jin-Fan</creator><creator>Lau, Wan Yee</creator><creator>Yang, Lian-Yue</creator><general>SAGE Publications</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130701</creationdate><title>Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma</title><author>Yang, Hao ; Chen, Guo-Dong ; Fang, Feng ; Liu, Zhen ; Hiu Yan Lau, Stephanie ; Zhang, Jin-Fan ; Lau, Wan Yee ; Yang, Lian-Yue</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-d9429e711757b6c5224c53cc2a1f154a18c199710846937ac2b6acf8cd6f88f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>alpha-Fetoproteins - metabolism</topic><topic>Biomarkers, Tumor - blood</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Intercellular Signaling Peptides and Proteins - blood</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Hao</creatorcontrib><creatorcontrib>Chen, Guo-Dong</creatorcontrib><creatorcontrib>Fang, Feng</creatorcontrib><creatorcontrib>Liu, Zhen</creatorcontrib><creatorcontrib>Hiu Yan Lau, Stephanie</creatorcontrib><creatorcontrib>Zhang, Jin-Fan</creatorcontrib><creatorcontrib>Lau, Wan Yee</creatorcontrib><creatorcontrib>Yang, Lian-Yue</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The International journal of biological markers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Yang, Hao</au><au>Chen, Guo-Dong</au><au>Fang, Feng</au><au>Liu, Zhen</au><au>Hiu Yan Lau, Stephanie</au><au>Zhang, Jin-Fan</au><au>Lau, Wan Yee</au><au>Yang, Lian-Yue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma</atitle><jtitle>The International journal of biological markers</jtitle><addtitle>Int J Biol Markers</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>28</volume><issue>3</issue><spage>286</spage><epage>297</epage><pages>286-297</pages><issn>0393-6155</issn><eissn>1724-6008</eissn><abstract>Background and aims
The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection.
Methods
One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured.
Results
The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival.
Conclusions
Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23568769</pmid><doi>10.5301/JBM.5000015</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged alpha-Fetoproteins - metabolism Biomarkers, Tumor - blood Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - pathology Female Humans Immunohistochemistry Intercellular Signaling Peptides and Proteins - blood Liver Neoplasms - blood Liver Neoplasms - pathology Male Middle Aged Prognosis Survival Analysis |
| title | Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma |
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