Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.

PURPOSE: To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage. EXPERIMENTAL DESIGN: MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed. RESULTS: MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred. CONCLUSIONS: Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas.

[Application of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma].

OBJECTIVE: To evaluate the usefulness of serum alpha-fetoprotein (AFP) in clinical diagnosis and screening for hepatocellular carcinoma (HCC). METHODS: Totally 290 HCC patients, 48 liver cirrhosis patients, and 49 healthy subjects were enrolled in this study. Serum AFP analysis was performed to investigate the correlation between the serum AFP level in HCC and the clinical or biochemical parameters of the disease, which included the size and number of tumor and the TNM stage. Sensitivities and specificities of AFP in HCC prediction at different cut-off levels were determined. RESULTS: The serum AFP level was significantly higher in HCC patients than in liver cirrhosis patients (P = 0.0274) and healthy subjects (P = 0.0001). Among 290 HCC patients, 95 patients (32.8%) were AFP-negative (AFP < 20 microg/L), 195 (67.2%) were AFP-positive (AFP > or =20 microg/L). Sensitivity and specificity of AFP at 20 microg/L cut-off was 67.2% and 29.2%, respectively, and the positive and negative predictive value was 85.2% and 12.8%, respectively. Sensitivity of AFP at 400 microg/L cut-off was only 42.8%. Serum AFP levels were significantly different among HCC with different tumor size (P = 0.0009), tumor number (P = 0.0001), and TNM stage [TNM I vs. TNM III-IV (P = 0.0001); TNM II vs. TNM III-IV (P = 0.0003)]. CONCLUSIONS: Increased serum AFP level is highly suggestive in HCC diagnosis. Combined with other imaging examinations, AFP level can be used for the screening of high risk population and for the follow-up of AFP-positive patients.