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Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma

 Seung Up Kim  ;  Jeon Han Park  ;  Hyon-Suk Kim  ;  Jae Myun Lee  ;  Hyun Gyu Lee  ;  Hyemi Kim  ;  Sung Hoon Choi  ;  Shinhwa Baek  ;  Beom Kyung Kim  ;  Jun Yong Park  ;  Do Young Kim  ;  Sang Hoon Ahn  ;  Jong Doo Lee  ;  Kwang-Hyub Han 
 YONSEI MEDICAL JOURNAL, Vol.56(5) : 1296-1306, 2015 
Journal Title
Issue Date
Area Under Curve ; Biomarkers/blood ; Biomarkers/metabolism ; Biomarkers, Tumor/blood ; Carcinoma, Hepatocellular/blood ; Carcinoma, Hepatocellular/diagnosis* ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins/blood* ; Intercellular Signaling Peptides and Proteins/metabolism* ; Liver Neoplasms/blood ; Liver Neoplasms/diagnosis* ; Male ; Middle Aged ; Protein Precursors/blood ; Protein Precursors/metabolism ; Prothrombin/metabolism ; ROC Curve ; Reverse Transcriptase Polymerase Chain Reaction/methods* ; Sensitivity and Specificity ; alpha-Fetoproteins/analysis ; alpha-Fetoproteins/metabolism
Dickkopf-1 ; biomarker ; hepatocellular carcinoma
PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/β-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Do Young(김도영)
Kim, Beom Kyung(김범경) ORCID logo https://orcid.org/0000-0002-5363-2496
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Park, Jun Yong(박준용) ORCID logo https://orcid.org/0000-0001-6324-2224
Baek, Sin Hwa(백신화)
Ahn, Sang Hoon(안상훈) ORCID logo https://orcid.org/0000-0002-3629-4624
Lee, Jae Myun(이재면) ORCID logo https://orcid.org/0000-0002-5273-3113
Lee, Jong Doo(이종두)
Han, Kwang-Hyub(한광협) ORCID logo https://orcid.org/0000-0003-3960-6539
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