Serum midkine is a more sensitive predictor for hepatocellular carcinoma than Dickkopf-1 and alpha-L-fucosidase in cirrhotic HCV patients

Abstract

Alpha fetoprotein (AFP) level is the gold standard diagnostic tool for detection and monitoring hepatocellular carcinoma (HCC) but with low sensitivity. Thus, the identification of alternative or combined serum markers of HCC is highly needed. Therefore, the aim of this work was to verify the value of serum midkine (MDK), Dickkopf-related protein 1 (DKK1), and alpha-L-fucosidase (AFU) in detection of HCC. We recruited 244 subjects to the present study; 89 with liver cirrhosis, 86 cirrhotic hepatitis C virus (HCV) induced HCC, and 69 apparently healthy volunteers as controls. Serum AFP, MDK, DKK1, and AFU were measured by ELISA. Patients with HCC showed significantly higher serum MDK, DKK1, and AFU levels compared with those patients with liver cirrhosis and healthy controls (X 2 = 179.56, 153.94, and 90.07 respectively) (P < .001 in all). In HCC cases, neither of MDK, DKK1, or AFU was correlated with tumor number. On the other hand, only serum DKK1 was significantly higher in lesions >5 cm, those with portal vein thrombosis and advanced HCC stage. Receiver operator characteristic (ROC) curve analysis showed that serum MDK levels discriminated between cirrhosis and HCC at a sensitivity of 100%, a specificity of 90% at cut-off value of >5.1 ng/mL. Although our results showed that serum MDK, DKK-1, and AFU are increased in HCC cases only MDK may be considered as the most promising serological marker for the prediction of the development of HCC in cirrhotic HCV patients.

HCC biomarkers – state of the old and outlook to future promising biomarkers and their potential in everyday clinical practice

“…The glycoprotein Dickkopf-1 (DKK-1), expressed mainly in the placenta and embryonic tissues, is an antagonist of the Wnt/β-catenin signaling pathway and is elevated in several cancer types. DKK-1 shows higher efficacy for detecting HCC than AFP in phase 4 trials ( 206 – 208 ), but midkine is more precise than DKK-1 in cirrhotic HCV patients ( 209 ). A combination of Golgi protein 73, AFP, and Dickkopf-1 increases the sensitivity and specificity of HCC detection ( 210 ).…”

“…Still, it is not specific to HCC, as high levels are also found in patients with diabetes, pancreatitis, and hypothyroidism ( 217 ). A retrospective phase 3 study with 280 HCC patients due to HBV B AFU shows good early detection prosperities of HCC ( 218 ), but midkine is a more sensitive predictor than AFU in HCC due to HCV ( 209 ). The combination of AFU with AFP raises sensitivity and specificity, especially in hepatitis-negative patients ( 219 ), but is worse than AFP alone in patients with HCC due to HBV ( 220 ).…”

Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma

“…In clinical practice, quantitation of serum alpha-fetoprotein (AFP) level and ultrasonography is widely used for the early detection of HCC [ 6 ]; however, the sensitivity and specificity of AFP detection at a cutoff value of 20 ng/mL are 59% and 90%, respectively [ 7 ]. Thus, novel biomarkers are required to facilitate a better diagnosis of HCC [ 8 ]. Biomarkers for treatment are also currently being explored [ 9 , 10 ].…”

Midkine (MDK) in Hepatocellular Carcinoma: More than a Biomarker

“…In another study, El-Shayeb et al [45] tested MDK serum levels in 89 patients with liver cirrhosis without HCC, 86 patients with cirrhotic HCV-induced HCC, and 69 healthy controls. They found serum MDK levels to be increased in HCC patients compared with the other two control groups.…”