原发性肝细胞癌中HBV各基因片段整合与癌基因、抑癌基因表达的相关研究

The corelation between integration of HSV X, S, Pre-S, C gene snd the expression of oncogenes/tumorsupressor genes in primary hepatocellujar carcinoma

目的研究肝细胞癌中ＨＢＶ各基因整台与癌基因、抑癌基因表达的关系。方法以随机引物法制备ＨＢＶ全基因及各基因探针，用Ｓｏｕｔｈｅｒｎ杂交测定ＨＢＶＤＮＡ的整台收志，以斑点杂交检查整台型ＨＣＣ中ＨＢＶ各基因的整台，以免疫组织细胞化学方法检查癌基因、抑癌基因的表达。结果３２例纯整台型ＨＣＣ中ＨＢＶＸ、Ｓ、Ｐｒｅ－Ｓ和Ｃ的整台率分别为８７５％（２／３２），６２．５％（２０／３２），６２．５％（２／３２），２５．０％（８／３２），其中ＨＢＶＸ基因整台率明显高于其它基因片段。３２例整台型ＨＣＣ中Ｐ６２ｍｙｃ、Ｐ２１ｒａｓ、Ｐ５３、Ｐ１６的检出率分别为８１．２％（２／３２），５０．０％（１６／３２），４３．８％（１４／３２）和３１３％（１０／３２），以Ｐ６２ｍｙｃ的检出率最高。统计学分析显示ＨＢＶＸ基因整合组Ｐ２１ｒａｓ、Ｐ６２ｍｙｃ及变异型Ｐ５３表达明显高于非整台组（Ｐ＜０．０５），ＨＢＶＰｒｅ－Ｓ整合组Ｐ６２ｍｙｃ的表达明显高于非整台组，其他ＨＢＶ基因整台与癌／抑癌基因的表达无明显相关性。结论ＨＢＶＸ基因在染色体上的整台与ｍｙｃ、ｒａｓ癌基因的活化及ｐ５３抑癌基因的失活关系密切，另外，Ｐｒｅ－Ｓ基因整台对ｍｙｃ的活化也?

Objective To study the relation between the integration of HBV X, S, Pre-S and Cgenes and the expression of oncogrnes/tumor suppressor gunes in hepatocellular carcinoma(HCC). MethodsTo prepare the Dig-HBV probes with random priming method, to detect the existing status of HBV DNAand the integration rates of HBV X, S, Pre-S and C gunes by Southern blot and dot blot hybridization,and to examine the expression of oncogenes and tumor suppressor genes by immunohistochemistry inHCC. Results The integration rates of HBV X, S, Pre-S and C gmes in HCC were 87.5%(28/32). 62.5%(20/32), 62.5%(20/32) and 25.0%(8/32), resistively. The expression rates of p62myc, p21ras p53 and pl6 proteinswere 81.2%(26/32), 50.0%(16/32), 43.8%(14/32), and 31.3(10/32), respectively. Statistical analysis showed thatthe expression of P62myc,, p21ras, and variant p53 proteins was obviously higher in HCC group with X genethan in free--X bine HCC group and that the expression of P62"y, protein was obviously higher in HCCgroup with Pre-S gene than in free-Pre-S HCC gfoup. Conclusion The integTation of HBV X or Pre-S genewith Cellular chromosome can activate myc, ras oncogrnes and inactivate the p53 tumor suppramr gene.