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

• Published in: Cancers Vol. 13; no. 8; p. 1828
• Main Authors: Kim, Si-Young, Lee, Hee-Seung, Bang, Seung-Min, Han, Dai-Hoon, Hwang, Ho-Kyoung, Choi, Gi-Hong, Chung, Moon-Jae, Kim, Seung-Up
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.04.2021; MDPI
• Subjects: Antigens; Biobanks; Biomarkers; Cancer; carbohydrate antigen 19-9; Cholangiocarcinoma; diagnosis; dickkopf-related protein 1; Dkk1 protein; Enzyme-linked immunosorbent assay; Hepatitis; Hospitals; intrahepatic cholangiocarcinoma; Medical prognosis; Medical screening; Patients; Public health; Software; Surgery; Tumors; United States > US; carbohydrate antigen 19-9; dickkopf-related protein 1; diagnosis; intrahepatic cholangiocarcinoma
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13081828

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, = 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 ( = 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, = 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.