title: Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Zhu
authors.forename: Jia-Jian
authors.initials: JJ
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Ju-Bo
authors.initials: JB
authors.lastname: Zhang
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Loffredo
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Xu-Jian
authors.initials: XJ
authors.lastname: Xing
authors.forename: Ning
authors.initials: N
authors.lastname: Ren
authors.forename: Qiong-Zhu
authors.initials: QZ
authors.lastname: Dong
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Zhou
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
authors.forename: Nai-Qing
authors.initials: NQ
authors.lastname: Zhao
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015331:Cohort Studies; D055088:Early Detection of Cancer; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000601:surgery; D000078792:Midkine; D009364:Neoplasm Recurrence, Local / Q000097:blood*; D009414:Nerve Growth Factors / Q000097:blood*; D012372:ROC Curve; D016896:Treatment Outcome; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C066254:MDK protein, human; D009414:Nerve Growth Factors; D000509:alpha-Fetoproteins; D000078792:Midkine