Mitotic checkpoint gene MAD1 in hepatocellular carcinoma is associated with tumor recurrence after surgical resection.
OBJECTIVE
Underlying mechanism of mitotic checkpoint gene mitosis arrest deficiency 1 (MAD1) in human hepatocellular carcinoma (HCC) is rarely known.


METHODS
We studied genetic change of the MAD1 gene as well as protein expression in 44 HCC and their associated non-cancerous surrounding liver tissues.


RESULTS
Genotype AG of MAD1 G-1849 A promoter was highly significant in microscopic vascular invasion than other genotypes (P = 0.006). Moreover, the mean tumor size of HCC with genotype AG (7.71 cm) was significantly larger than those of other genotypes (AA, 4.41 cm; GG, 4.59 cm; P = 0.033). After a median follow-up of 22 months, 18 (41%) of the 44 patients relapsed. Eleven (32.4%) of 34 with MAD1 protein expression and 7 (70%) of 10 with no expression of MAD1 protein showed tumor recurrence. The incidence of tumor recurrence in patients with the lost MAD1 expression was significantly higher than in those with the expressed MAD1 protein (P = 0.011).


CONCLUSIONS
These results suggest that MAD1 promoter genotype may be involved in tumor progression. Moreover, the loss of MAD1 protein expression may be related to the tumor recurrence after surgical resection of HCC.
Nam
Chang Woo
CW
Department of Surgery, University of Ulsan College of Medicine, Biomedical Research Center, Ulsan University Hospital, Dong-Gu, Ulsan, Korea.
Park
Neung Hwa
NH
Park
Bo Ryung
BR
Shin
Jung Woo
JW
Jung
Seok Won
SW
Na
Yang Won
YW
Seo
Jae Hee
JH
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; D009687:Nuclear Proteins