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Serum Dickkopf-1 in Combined with CA 19-9 as a Biomarker of Intrahepatic Cholangiocarcinoma

 Si-Young Kim  ;  Hee-Seung Lee  ;  Seung-Min Bang  ;  Dai-Hoon Han  ;  Ho-Kyoung Hwang  ;  Gi-Hong Choi  ;  Moon-Jae Chung  ;  Seung-Up Kim 
 CANCERS, Vol.13(8) : 1828, 2021-04 
Journal Title
Issue Date
carbohydrate antigen 19-9 ; diagnosis ; dickkopf-related protein 1 ; intrahepatic cholangiocarcinoma
Dickkopf-related protein 1 (DKK-1) has a diagnostic and prognostic value in various malignant tumors. We investigated the diagnostic and prognostic performance of DKK-1 in combination with carbohydrate antigen 19-9 (CA 19-9) in cholangiocarcinoma (CCC) patients. Serum DKK-1 levels were measured using enzyme-linked immunosorbent assay. The receiver operating characteristic (ROC) curve, area under ROC (AUROC) analyses, Kaplan-Meier method, and Cox proportional hazard model were used to evaluate the diagnostic and prognostic performance of DKK-1 in combination with CA 19-9. We checked DKK-1 levels in 356 CCC patients and found that DKK-1 was significantly elevated only in 79 intrahepatic CCC (ICC) patients compared to controls (340.5 vs. 249.8 pg/mL, p = 0.002). The optimal cutoff level of DKK-1 used to identify ICC patients was 258.0 pg/mL (AUROC = 0.637, sensitivity = 59.5%, specificity = 56.9%, positive predictive value (PPV) = 40.5%, negative predictive value (NPV) = 74.0%, positive likelihood ratio (LR) = 1.38, and negative LR = 0.71). Using this cutoff, 47 (59.5%) patients were correctly diagnosed with ICC. DKK-1 in combination with CA 19-9 showed a better diagnostic performance (AUROC = 0.793, sensitivity = 74.7%, specificity = 56.3%, PPV = 45.7, NPV = 81.8, positive LR = 1.71, and negative LR = 0.45) than CA 19-9 alone. The low DKK-1 and CA 19-9 expression group had a significantly longer overall survival (OS) than the high expression group (p = 0.006). The higher level of DKK-1 and CA 19-9 was independently associated with shorter OS (hazard ratio = 3.077, 95% confidence interval 1.389-6.819, p = 0.006). The diagnostic and prognostic performance of DKK-1 in combination with CA 19-9 might be better than those of CA 19-9 alone in ICC patients.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Up(김승업) ORCID logo https://orcid.org/0000-0002-9658-8050
Kim, Si-Young(김시영)
Bang, Seungmin(방승민) ORCID logo https://orcid.org/0000-0001-5209-8351
Lee, Hee Seung(이희승) ORCID logo https://orcid.org/0000-0002-2825-3160
Chung, Moon Jae(정문재) ORCID logo https://orcid.org/0000-0002-5920-8549
Choi, Gi Hong(최기홍) ORCID logo https://orcid.org/0000-0002-1593-3773
Han, Dai Hoon(한대훈) ORCID logo https://orcid.org/0000-0003-2787-7876
Hwang, Ho Kyoung(황호경) ORCID logo https://orcid.org/0000-0003-4064-7776
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