细胞色素C及相关细胞凋亡蛋白、基因在原发性肝癌组织表达的临床意义

The expressions and clinical significances of Cytochrome C and related apoptosis protein or gene in primary hepatocellular carcinoma

目的观察外源性凋亡通路中Caspase8和Bid及内源性凋亡通路中Bcl-2、Bax、细胞色素C(Cyt-C)和Cas-pase9在50例原发性肝细胞癌(肝癌组)及30例正常肝组织(对照组)中的表达,并分析其与病理分期、肿瘤分化程度和淋巴结转移的关系。方法应用免疫组织化学方法检测Bax表达,应用核酸原位分子杂交方法检测Caspase8、Bid、Bcl-2、Cyt-C和Caspase9表达。结果 Caspase8表达强度与对照组比较呈升高趋势(P<0.05),阳性表达率组间差异未见统计学意义(P>0.05)。Bid阳性表达率与对照组比较呈下降趋势(P<0.01),表达强度两组间差异未见统计学意义(P>0.05)。Bcl-2阳性表达率和表达强度较对照组均明显下降(P<0.01),Bax阳性表达率和表达强度较对照组均下降(P<0.05和P<0.01)。Cyt-C和Caspase9的阳性表达率和表达强度两组间比较差异均未见统计学意义(P>0.05)。高、中分化肝癌组Cyt-C阳性表达率均明显高于低分化肝癌组(P<0.05和P<0.01),但其与病理分级和淋巴结转移未见相关性(P>0.05)。Caspase8、Bid、Bcl-2、Bax和Caspase9在不同病理分级、肿瘤分化程度和淋巴结转移组中表达差异均未见统计学意义(P>0.05)。结论在肝癌发生发展过程中,早期外源性凋亡通路发挥促凋亡活性,而随着肿瘤分化程度的降低,内源性凋亡通路发挥抗凋亡活性,且Cyt-C的表达调节应该是一晚期事件。

Objective To observe the expressions of Caspase8,Bid which located in extrinsic apoptosis pathway and Bcl-2,Bax,Cytochrome C（Cyt-C）,Caspase9 which located in intrinsic apoptosis pathway in 50 cases primary hepatocellular carcinoma（HCC group）and 30 cases normal liver specimen（control group）,then to analyze their relationships with pathological grades,tumor differentiation and lymph node metastasis.Methods To detect the expression of Bax by immunohistochemistry,and to detect the expressions of Caspase8,Bid,Bcl-2,Cyt-C and Caspase9 by nucleic acid hybridization in situ.Results The expression intensity of Caspase8 enhanced in HCC compared with control group（P0.05）,whereas the positive expression rate of Caspase8 had no different significance between two groups（P0.05）.The positive expression rate of Bid decreased（P0.01）,but the expression intensity had no different significance between two groups（P0.05）.The positive expression rate and expression intensity of Bcl-2 decreased in HCC group compared with control group（both P0.01）.The positive expression rate and expression intensity of Bax decreased in HCC group compared with control group（P0.05and0.01）.The positive expression rates and intensities of Cyt-C and Caspase 9 didn＇t have different significances between two groups（all P0.05）.The positive expressions of Cyt-C in high differentiation and middle differentiation groups were higher than which in low differentiation group,and there were different significances（P0.01and0.05）,however,the expressions of Cyt-C had no relationship with pathological grade and lymph node metastasis.The expressions of Caspase8,Bid,Bcl-2,Bax and Caspase9 didn＇t have different significances in different pathological grade,tumor differentiation and lymph node metastasis groups（all P0.05）.Conclusion During the development and progression of HCC,the extrinsic apoptosis pathway plays a pro-apoptosis role in the early stage,but with the decreasing of tumor differentiation level,the intrinsic apoptosis pathway plays an anti-apoptosis role.The regulation of Cyt-C＇s expression ought to be a late event in HCC.