Epigenetic methylation and expression of caspase 8 and survivin in hepatocellular carcinoma.
Caspase 8 and survivin are known as key molecules of apoptosis in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the relationship between promoter methylation and expression and apoptotic function of caspase 8 and survivin in HCC. Promoter methylation of the caspase 8 and survivin gene was analyzed in 73 primary HCC using methylation-specific polymerase chain reaction. The relationship between immunohistochemical expression of gene products and proliferative/apoptotic indices, and clinicopathological parameters was also investigated. Twenty-five (34%) and 24 (33%) patients had promoter methylation of caspase 8 and survivin gene. Immunohistochemical staining of caspase 8 and survivin was observed in 35 (48%) and 32 (44%). The methylation of caspase 8 and survivin demonstrated a negative correlation with immunohistochemical expression of gene products (P= 0.049 and P= 0.001). Methylation of caspase 8 and positive expression of its gene product was significantly correlated with high apoptotic indices (P= 0.032 and P= 0.026). Nuclear survivin expression was significantly correlated with high proliferative index (P= 0.001). On survival analysis, positive nuclear survivin expression was associated with a poor prognosis in HCC (P= 0.043). In conclusion, epigenetic alteration by promoter methylation of caspase 8 and survivin may constitute an important regulatory mechanism for expression of those genes in HCC.
Cho
Seok
S
Department of Internal Medicine, Center of Digestive Disease, Chonnam National University Hospital and Medical School, Hakdong 8, Dongku, Gwangju 501-757, South Korea.
Lee
Jae Hyek
JH
Cho
Sung Bum
SB
Yoon
Kyeng Won
KW
Park
Seon Young
SY
Lee
Wan Sik
WS
Park
Chang Hwan
CH
Joo
Young Eun
YE
Kim
Hyun Soo
HS
Choi
Sung Kyu
SK
Rew
Jong Sun
JS
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053181:Caspase 8 / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D053181:Caspase 8