Original Articles
Copyright ©The Author(s) 2000. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2000; 6(3): 356-360
Published online Jun 15, 2000. doi: 10.3748/wjg.v6.i3.356
Analysis of in vivo patterns of caspase 3 gene expression in primary hepatocellular carcinoma and its relationship to p21WAF1 expression and hepatic apoptosis
Bao-Hua Sun, Jun Zhang, Bao-J Wang, Xi-Ping Zhao, You-Kun Wang, Zhi-Qun Yu, Lian-Jie Hao, Dong-Liang Yang
Bao-Hua Sun, Jun Zhang, Bao-J Wang, Xi-Ping Zhao, You-Kun Wang, Zhi-Qun Yu, Dong-Liang Yang, Lian-Jie Hao, Department of Clinical Immunology, Tongji Hospital, Tongji Medical University, Wuhan 430030, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Dong-Liang Yang, Department of Clinical Immunology, Tongji Hospital, Tongji Medical University, Wuhan 430030, Hubei Province, China. bhsun@yahoo.com
Telephone: +86-27-83662570
Received: January 1, 2000
Revised: January 8, 2000
Accepted: January 15, 2000
Published online: June 15, 2000
Abstract

AIM: To detect the expression of caspase 3 gene in primary huma n hepatocellular carcinoma (HCC) and investigate its relationship to p21WAF1 gene expression and HCC apoptosis.

METHODS: In situ hybridization was employed to determine caspase 3 and p21WAF1 expression in HCC. In situ end-labeling was used to detect hepatocytic apoptosis in HCC.

RESULTS: Twenty-one of 39 (53.8%) cases of HCC were found to express caspase 3 transcripts, while 46.2% of HCC failed to express caspase 3. Non-cancerous adjacent liver tissues showed more positive caspase 3 (87.5%, 7/8) as compared with HCC (P < 0.05). The expression of caspase 3 is correlated with HCC differentiation, 72.2% (13/18) of moderately to highly differentiated HCC showed caspase 3 transcripts positive, while only 38.1% of poorly differentiated HCC harbored caspase 3 transcripts (P < 0.05). No relationship was found between caspase 3 expression and tumor size or grade or metastasis, although 62.5% (5/8) of HCC with metastasis were caspase 3 positive and a little higher than that with no metastasis (51.6%, P > 0.05). Expression of caspase 3 alone did not affect the apoptosis index (AI) of HCC. The AI was 7.12‰ in caspase 3-positive tumors (n = 21), while in caspase 3-negative cases (n = 18) 6.59‰ (P > 0.05). Expression of caspase 3 clearly segregated with p21WAF1 positive tumors as compared with p21WAF1 negative cases (16 of 23, 69.6% vs 5 of 16, 31.3%) with statistical significance(P = 0.017). In the cases with positive caspase 3 and negative p21WAF1, the AI was found slightly higher, but with no statistical significance, than that with expression of p21WAF1 and caspase 3 (7.21‰vs 6.98‰, P > 0.05).

CONCLUSION: Loss of caspase 3 expression may contribute to HCC carcinogenesis, although the expression of caspase 3 does not correlate well with cell apoptosis in HCC. p21WAF1 may be merely one of the inhibitors which can reduce caspase 3 mediated cell apoptosis in HCCs.

Keywords: carcinoma, hepatocellular; caspase 3; apoptosis; liver neoplasms; gene expression