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

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13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1296-1306
Number of pages11
JournalYonsei medical journal
Volume56
Issue number5
DOIs
Publication statusPublished - 2015 Sep 1

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

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