Objective: To explore the feasibility of alpha-fetoproteins (alpha-FP) mRNA and melanoma antigen-1 (MAGE-1) mRNA as 2 markers of micrometastasis in hepatocellular carcinoma (HCC) patients' peripheral blood.
Methods: Subjects were divided into five groups: patients with HCC (n=65); patients with hepatitisB and liver cirrhosis (n=22); patients with metastatic liver cancer (n=12); patients with hepatic hemangioma (n=12); and healthy volunteers (n=20). alpha-FP mRNA and MAGE-1 mRNA in peripheral blood were tested by nested reverse transcription polymerase chain reaction (RT-PCR).
Results: MAGE-1 mRNA and alpha-FP mRNA were detected in 27 (42%) and 35 (54%) of 65 HCC patients respectively, while 42 (65%) HCC patients were positive for at least 1 marker. The frequency of alpha-FP mRNA and MAGE-1 mRNA positivity strongly correlated with portal thrombosis, intrahepatic metastatic nodules, tumor diameter and TNM stage (P <0.05). With regard to controls, 4 of 12 (33%) samples from patients with metastatic liver cancer showed MAGE-1 mRNA in their peripheral blood, but groups of hepatitis and cirrhosis, hepatic hemangioma, healthy volunteers did not. And 3 of 22 samples (14%) from group hepatitis and cirrhosis showed alpha-FP mRNA, but none of samples from other control group showed alpha-FP mRNA.
Conclusions: Nested RT-PCR is a sensitive and reliable method for detecting circulating HCC cells. Two-marker RT-PCR assay with a liver-specific alpha-FP marker in combination with a cancer-specific MAGE-1 marker may be a promising tool for detecting micrometastases with better sensitivity and specificity than one marker RT-PCR.