Circulating mage-1 andmage-3 transcripts as tumour-specific markers for hepatocellular carcinoma

ABSTRACT

The members of human Melanoma Associated Antigen [MAGE] gene family are highly expressed in human hepatocellular carcinoma [HCC]. The present study aimed to detect tumour cells in the peripheral blood of HCC patients by using mRNA of the MAGE-1 and MAGE-3 genes as specific tumour markers. This study was carried out on 100 subjects included in three groups; group I HCC patients [n=50], group II cirrhotic patients [n=25] and group III apparently healthy subjects as controls [n=25]. Patients of groups I and II were attendants of the Out Patient Clinics of National Liver Institute, Menoufiya University. The mRNA of the MAGE-1 and MAGE-3 genes in peripheral blood mononuclear cells [PBMC] was detected by using nested RT-PCR. Results revealed that of the 50 HCC patients, MAGE-1 and MAGE-3 mRNA were positive in 56% [28/50] and 46% [23/50] of PBMC respectively and 64% [32/50] of HCC samples were detected to express at least one type of MAGE mRNA. The detection of MAGE transcripts in PBMC was correlated with the advanced stages and the tumour size of HCC as 92.9% [26/28] and 100% [23/23] of positive MAGE-1 and MAGE-3 transcripts respectively were detected in HCC cases in stages III and VI. Also, 100% of positive MAGE-1 and MAGE-3 mRNA detected were related to HCC cases having sizes > 4cm. In addition, expression of MAGE-3 was correlated to the evidences of metastasis. On the other hand, detection of MAGE-1 and/or MAGE-3 transcripts was not detected in the PBMC of cirrhotic patients or in the PBMC of healthy controls. No statistical significant correlation was observed between the expression of MAGE genes and the increased levels of alphafoeto protein [AFP], the presence of liver cirrhosis or viral hepatitis. Therefore, these tumour specific antigens can be used as molecular markers for early diagnosis and possible targets for immunotherapy for patients with HCC