Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma.
10.3349/ymj.2015.56.5.1296
- Author:
Seung Up KIM
1
;
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
Author Information
1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. gihankhys@yuhs.ac
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Dickkopf-1;
hepatocellular carcinoma;
biomarker
- MeSH:
Area Under Curve;
Biomarkers/blood/metabolism;
Biomarkers, Tumor/blood;
Carcinoma, Hepatocellular/blood/*diagnosis;
Enzyme-Linked Immunosorbent Assay;
Female;
Humans;
Intercellular Signaling Peptides and Proteins/*blood/*metabolism;
Liver Neoplasms/blood/*diagnosis;
Male;
Middle Aged;
Protein Precursors/blood/metabolism;
Prothrombin/metabolism;
ROC Curve;
Reverse Transcriptase Polymerase Chain Reaction/*methods;
Sensitivity and Specificity;
alpha-Fetoproteins/analysis/metabolism
- From:Yonsei Medical Journal
2015;56(5):1296-1306
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-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.
