Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma
To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage. MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or li...
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Veröffentlicht in: | Clinical cancer research 2013-07, Vol.19 (14), p.3944-3954 |
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creator | ZHU, Wen-Wei GUO, Jia-Jian NING REN DONG, Qiong-Zhu ZHOU, Hai-Jun REN, Zheng-Gang ZHAO, Nai-Qing XIN WEI WANG TANG, Zhao-You QIN, Lun-Xiu YE, Qing-Hai LEI GUO JIA, Hu-Liang MING ZHU ZHANG, Ju-Bo LOFFREDO, Christopher A FORGUES, Marshonna HUA HUANG XING, Xu-Jian |
description | To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas. |
doi_str_mv | 10.1158/1078-0432.ccr-12-3363 |
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MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.</description><identifier>ISSN: 1078-0432</identifier><identifier>ISSN: 1557-3265</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.ccr-12-3363</identifier><identifier>PMID: 23719264</identifier><identifier>CODEN: CCREF4</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>alpha-Fetoproteins - metabolism ; Antineoplastic agents ; Biological and medical sciences ; Biomarkers, Tumor - blood ; Carcinoma, Hepatocellular - blood ; Carcinoma, Hepatocellular - diagnosis ; Carcinoma, Hepatocellular - surgery ; Case-Control Studies ; Cell Line, Tumor ; Cohort Studies ; Early Detection of Cancer ; Gastroenterology. Liver. Pancreas. Abdomen ; Humans ; Liver Neoplasms - blood ; Liver Neoplasms - diagnosis ; Liver Neoplasms - surgery ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Midkine ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Neoplasm Recurrence, Local - blood ; Nerve Growth Factors - blood ; Pharmacology. Drug treatments ; ROC Curve ; Treatment Outcome ; Tumors ; Up-Regulation</subject><ispartof>Clinical cancer research, 2013-07, Vol.19 (14), p.3944-3954</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-2bee8cf2dfb8204f3551d64d4ad09ff81e7f41dbd3fa0823bce8d395c541b68a3</citedby><cites>FETCH-LOGICAL-c507t-2bee8cf2dfb8204f3551d64d4ad09ff81e7f41dbd3fa0823bce8d395c541b68a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,3343,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27947815$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23719264$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>ZHU, Wen-Wei</creatorcontrib><creatorcontrib>GUO, Jia-Jian</creatorcontrib><creatorcontrib>NING REN</creatorcontrib><creatorcontrib>DONG, Qiong-Zhu</creatorcontrib><creatorcontrib>ZHOU, Hai-Jun</creatorcontrib><creatorcontrib>REN, Zheng-Gang</creatorcontrib><creatorcontrib>ZHAO, Nai-Qing</creatorcontrib><creatorcontrib>XIN WEI WANG</creatorcontrib><creatorcontrib>TANG, Zhao-You</creatorcontrib><creatorcontrib>QIN, Lun-Xiu</creatorcontrib><creatorcontrib>YE, Qing-Hai</creatorcontrib><creatorcontrib>LEI GUO</creatorcontrib><creatorcontrib>JIA, Hu-Liang</creatorcontrib><creatorcontrib>MING ZHU</creatorcontrib><creatorcontrib>ZHANG, Ju-Bo</creatorcontrib><creatorcontrib>LOFFREDO, Christopher A</creatorcontrib><creatorcontrib>FORGUES, Marshonna</creatorcontrib><creatorcontrib>HUA HUANG</creatorcontrib><creatorcontrib>XING, Xu-Jian</creatorcontrib><title>Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.</description><subject>alpha-Fetoproteins - metabolism</subject><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - blood</subject><subject>Carcinoma, Hepatocellular - blood</subject><subject>Carcinoma, Hepatocellular - diagnosis</subject><subject>Carcinoma, Hepatocellular - surgery</subject><subject>Case-Control Studies</subject><subject>Cell Line, Tumor</subject><subject>Cohort Studies</subject><subject>Early Detection of Cancer</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Humans</subject><subject>Liver Neoplasms - blood</subject><subject>Liver Neoplasms - diagnosis</subject><subject>Liver Neoplasms - surgery</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Midkine</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Neoplasm Recurrence, Local - blood</subject><subject>Nerve Growth Factors - blood</subject><subject>Pharmacology. Drug treatments</subject><subject>ROC Curve</subject><subject>Treatment Outcome</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>1078-0432</issn><issn>1557-3265</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctu1TAQhi0EouXAI4C8QWKT4vElcTZIEHpBaoVoYW1NfCmmOfHBTirx9iTqaaGrGWm--WfmH0JeAzsCUPo9sEZXTAp-ZG2ugFdC1OIJOQSlmkrwWj1d8nvmgLwo5RdjIIHJ5-SAiwZaXstD8u34FocZp5hGmgK9iO4mjp5ioUg_R7weU5mipVc-z1v6KaYt5hufaRzpmd_hlKwfhnnATDvMNo5L_SV5FnAo_tU-bsiPk-Pv3Vl1_vX0S_fxvLKKNVPFe--1DdyFXnMmg1AKXC2dRMfaEDT4JkhwvRMBmeait1470SqrJPS1RrEhH-50d3O_9c76cco4mF2Oy45_TMJoHlfG-NNcp1tTC5CyhUXg3V4gp9-zL5PZxrLeg6NPczEgBdSilcvwDVF3qM2plOzDwxhgZn2HWa02q9Wm6y4NcLO-Y-l78_-OD133_i_A2z2AxeIQMo42ln9c08pGgxJ_AT1ZlT0</recordid><startdate>20130715</startdate><enddate>20130715</enddate><creator>ZHU, Wen-Wei</creator><creator>GUO, Jia-Jian</creator><creator>NING REN</creator><creator>DONG, Qiong-Zhu</creator><creator>ZHOU, Hai-Jun</creator><creator>REN, Zheng-Gang</creator><creator>ZHAO, Nai-Qing</creator><creator>XIN WEI WANG</creator><creator>TANG, Zhao-You</creator><creator>QIN, Lun-Xiu</creator><creator>YE, Qing-Hai</creator><creator>LEI GUO</creator><creator>JIA, Hu-Liang</creator><creator>MING ZHU</creator><creator>ZHANG, Ju-Bo</creator><creator>LOFFREDO, Christopher A</creator><creator>FORGUES, Marshonna</creator><creator>HUA HUANG</creator><creator>XING, Xu-Jian</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><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><scope>5PM</scope></search><sort><creationdate>20130715</creationdate><title>Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma</title><author>ZHU, Wen-Wei ; GUO, Jia-Jian ; NING REN ; DONG, Qiong-Zhu ; ZHOU, Hai-Jun ; REN, Zheng-Gang ; ZHAO, Nai-Qing ; XIN WEI WANG ; TANG, Zhao-You ; QIN, Lun-Xiu ; YE, Qing-Hai ; LEI GUO ; JIA, Hu-Liang ; MING ZHU ; ZHANG, Ju-Bo ; LOFFREDO, Christopher A ; FORGUES, Marshonna ; HUA HUANG ; XING, Xu-Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c507t-2bee8cf2dfb8204f3551d64d4ad09ff81e7f41dbd3fa0823bce8d395c541b68a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>alpha-Fetoproteins - metabolism</topic><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - blood</topic><topic>Carcinoma, Hepatocellular - blood</topic><topic>Carcinoma, Hepatocellular - diagnosis</topic><topic>Carcinoma, Hepatocellular - surgery</topic><topic>Case-Control Studies</topic><topic>Cell Line, Tumor</topic><topic>Cohort Studies</topic><topic>Early Detection of Cancer</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Humans</topic><topic>Liver Neoplasms - blood</topic><topic>Liver Neoplasms - diagnosis</topic><topic>Liver Neoplasms - surgery</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Midkine</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Neoplasm Recurrence, Local - blood</topic><topic>Nerve Growth Factors - blood</topic><topic>Pharmacology. Drug treatments</topic><topic>ROC Curve</topic><topic>Treatment Outcome</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ZHU, Wen-Wei</creatorcontrib><creatorcontrib>GUO, Jia-Jian</creatorcontrib><creatorcontrib>NING REN</creatorcontrib><creatorcontrib>DONG, Qiong-Zhu</creatorcontrib><creatorcontrib>ZHOU, Hai-Jun</creatorcontrib><creatorcontrib>REN, Zheng-Gang</creatorcontrib><creatorcontrib>ZHAO, Nai-Qing</creatorcontrib><creatorcontrib>XIN WEI WANG</creatorcontrib><creatorcontrib>TANG, Zhao-You</creatorcontrib><creatorcontrib>QIN, Lun-Xiu</creatorcontrib><creatorcontrib>YE, Qing-Hai</creatorcontrib><creatorcontrib>LEI GUO</creatorcontrib><creatorcontrib>JIA, Hu-Liang</creatorcontrib><creatorcontrib>MING ZHU</creatorcontrib><creatorcontrib>ZHANG, Ju-Bo</creatorcontrib><creatorcontrib>LOFFREDO, Christopher A</creatorcontrib><creatorcontrib>FORGUES, Marshonna</creatorcontrib><creatorcontrib>HUA HUANG</creatorcontrib><creatorcontrib>XING, Xu-Jian</creatorcontrib><collection>Pascal-Francis</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ZHU, Wen-Wei</au><au>GUO, Jia-Jian</au><au>NING REN</au><au>DONG, Qiong-Zhu</au><au>ZHOU, Hai-Jun</au><au>REN, Zheng-Gang</au><au>ZHAO, Nai-Qing</au><au>XIN WEI WANG</au><au>TANG, Zhao-You</au><au>QIN, Lun-Xiu</au><au>YE, Qing-Hai</au><au>LEI GUO</au><au>JIA, Hu-Liang</au><au>MING ZHU</au><au>ZHANG, Ju-Bo</au><au>LOFFREDO, Christopher A</au><au>FORGUES, Marshonna</au><au>HUA HUANG</au><au>XING, Xu-Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2013-07-15</date><risdate>2013</risdate><volume>19</volume><issue>14</issue><spage>3944</spage><epage>3954</epage><pages>3944-3954</pages><issn>1078-0432</issn><issn>1557-3265</issn><eissn>1557-3265</eissn><coden>CCREF4</coden><abstract>To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>23719264</pmid><doi>10.1158/1078-0432.ccr-12-3363</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research; Alma/SFX Local Collection |
subjects | alpha-Fetoproteins - metabolism Antineoplastic agents Biological and medical sciences Biomarkers, Tumor - blood Carcinoma, Hepatocellular - blood Carcinoma, Hepatocellular - diagnosis Carcinoma, Hepatocellular - surgery Case-Control Studies Cell Line, Tumor Cohort Studies Early Detection of Cancer Gastroenterology. Liver. Pancreas. Abdomen Humans Liver Neoplasms - blood Liver Neoplasms - diagnosis Liver Neoplasms - surgery Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Midkine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Recurrence, Local - blood Nerve Growth Factors - blood Pharmacology. Drug treatments ROC Curve Treatment Outcome Tumors Up-Regulation |
title | Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma |
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