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
Hauptverfasser: 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
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container_end_page 3954
container_issue 14
container_start_page 3944
container_title Clinical cancer research
container_volume 19
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.
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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. 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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. 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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><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. 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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. 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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.</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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