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

Kim SU, Park JH, Kim HS, Lee JM, Lee HG, Kim H, Choi SH, Baek S, Kim BK, Park JY, Kim do Y, Ahn SH, Lee JD, Han KH - Yonsei Med. J. (2015)

Bottom Line: 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).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).Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Knock-down of DKK-1 inhibits cell growth. (A) DKK-1 knock-down in Huh7 cells decreased the amount of secreted DKK-1 after 48 h, determined by ELISA. (B) DKK-1 knock-down inhibited Huh7 cell growth after 48 h, determined by MTT assays. *p<0.01. DKK-1, dickkopf-1.
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Figure 3: Knock-down of DKK-1 inhibits cell growth. (A) DKK-1 knock-down in Huh7 cells decreased the amount of secreted DKK-1 after 48 h, determined by ELISA. (B) DKK-1 knock-down inhibited Huh7 cell growth after 48 h, determined by MTT assays. *p<0.01. DKK-1, dickkopf-1.

Mentions: Wound healing assays showed that DKK-1 overexpression efficiently promoted migration of 293 cells (Fig. 2A), whereas DKK-1 knock-down significantly inhibited Huh7 cell migration (Fig. 2B) compared with mock controls. Similarly, invasion assays with Huh7 cells showed that DKK-1 overexpression promoted invasion, whereas DKK-1 knock-down inhibited the invasion (Fig. 2C). MTT assays showed that the DKK-1 knock-down significantly inhibited Huh7 cell growth after 48 h, and the amount of secreted DKK-1 significantly decreased (Fig. 3).


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

Kim SU, Park JH, Kim HS, Lee JM, Lee HG, Kim H, Choi SH, Baek S, Kim BK, Park JY, Kim do Y, Ahn SH, Lee JD, Han KH - Yonsei Med. J. (2015)

Knock-down of DKK-1 inhibits cell growth. (A) DKK-1 knock-down in Huh7 cells decreased the amount of secreted DKK-1 after 48 h, determined by ELISA. (B) DKK-1 knock-down inhibited Huh7 cell growth after 48 h, determined by MTT assays. *p<0.01. DKK-1, dickkopf-1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4541659&req=5

Figure 3: Knock-down of DKK-1 inhibits cell growth. (A) DKK-1 knock-down in Huh7 cells decreased the amount of secreted DKK-1 after 48 h, determined by ELISA. (B) DKK-1 knock-down inhibited Huh7 cell growth after 48 h, determined by MTT assays. *p<0.01. DKK-1, dickkopf-1.
Mentions: Wound healing assays showed that DKK-1 overexpression efficiently promoted migration of 293 cells (Fig. 2A), whereas DKK-1 knock-down significantly inhibited Huh7 cell migration (Fig. 2B) compared with mock controls. Similarly, invasion assays with Huh7 cells showed that DKK-1 overexpression promoted invasion, whereas DKK-1 knock-down inhibited the invasion (Fig. 2C). MTT assays showed that the DKK-1 knock-down significantly inhibited Huh7 cell growth after 48 h, and the amount of secreted DKK-1 significantly decreased (Fig. 3).

Bottom Line: 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).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).Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus