Quantitative analysis of apoptosis‐related gene expression in hepatocellular carcinoma

BACKGROUND The suppression of apoptosis is an important factor in tumor progression in hepatocellular carcinoma (HCC). However, to the authors knowledge the clinicopathologic importance of the expression of apoptosis‐related genes (bcl‐2, bax, and survivin) in HCC remains unclear. In the current stu...

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Bibliographic Details
Published in:Cancer 2002-11, Vol.95 (9), p.1938-1945
Main Authors: Ikeguchi, Masahide, Hirooka, Yasuaki, Kaibara, Nobuaki
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm - genetics
apoptosis
Apoptosis - genetics
bax
bcl-2-Associated X Protein
bcl‐2
Biological and medical sciences
Blotting, Western
Carcinoma, Hepatocellular - genetics
Carcinoma, Hepatocellular - pathology
Cell Division
disease recurrence
Female
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression
Genes, bcl-2
Glyceraldehyde-3-Phosphate Dehydrogenases - genetics
Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism
hepatocellular carcinoma (HCC)
Humans
Immunohistochemistry
Inhibitor of Apoptosis Proteins
Liver - metabolism
Liver Neoplasms - genetics
Liver Neoplasms - pathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Microtubule-Associated Proteins - genetics
Middle Aged
Neoplasm Proteins
Neoplasm Recurrence, Local
Prognosis
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-bcl-2
real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR)
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
survivin
Tumor Cells, Cultured - pathology
Tumors
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Summary:BACKGROUND The suppression of apoptosis is an important factor in tumor progression in hepatocellular carcinoma (HCC). However, to the authors knowledge the clinicopathologic importance of the expression of apoptosis‐related genes (bcl‐2, bax, and survivin) in HCC remains unclear. In the current study, the authors investigated the correlation between expression of apoptosis‐related genes and the occurrence of spontaneous apoptosis in HCC. In addition, the prognostic significance of the expression of apoptosis‐related genes in patients with HCC was analyzed. METHODS Tissue samples were obtained through surgical resection of the liver in 53 patients with HCC and 5 patients without HCC. The expression levels of bcl‐2, bax, survivin, and glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA were analyzed using real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR). The bcl‐2/bax ratio and survivin/GAPDH ratio of the tumors were compared with clinicopathologic findings. In addition, apoptotic tumor cells and the proliferative activity of tumor cells were detected using immunohistochemistry. RESULTS The bcl‐2/bax ratios of the tumors were not different from those of noncancerous liver tissue samples obtained from regions distant from the tumors and were not found to correlate with apoptosis or with clinical importance in HCC. In contrast, the survivin/GAPDH ratios of the tumors were significantly higher than those of noncancerous liver tissue and demonstrated a negative correlation with apoptosis and a positive correlation with the proliferative activity of tumor cells. Moreover, patients who had tumors with a high survivin/GAPDH ratio were found to have a high incidence of disease recurrence. CONCLUSIONS The real‐time RT‐PCR method appears to be a useful technique with which to detect reliable gene expression in tissues, and the detection of survivin mRNA expression by this method may be a useful marker for identifying patients with HCC who have a high risk of disease recurrence. Cancer 2002;95:1938–45. © 2002 American Cancer Society. DOI 10.1002/cncr.10898 In patients with hepatocellular carcinoma, bcl‐2 or bax messenger RNA expression did not correlate with apoptosis, whereas survivin messenger RNA expression was found to correlate negatively with the occurrence of apoptosis. Moreover, messenger RNA expression of survivin was found to be correlated positively with poor patient survival.
ISSN:0008-543X
1097-0142
DOI:10.1002/cncr.10898