肝病患者血清肿瘤标记物含量及肿瘤坏死因子相关凋亡诱导配体受体表达在癌变中的临床意义

Alteration of serous tumor marker and the expression of TRAIL receptors correlated with the development of hepatoma

目的探讨血浆透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型胶原(ⅢC)、Ⅳ型胶原(ⅣC)、甲胎蛋白(AFP)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)受体-2(DR5)、诱捕受体-1(DcR1)的表达与肝纤维化及肝癌变的关系。方法用ELISA方法测定正常对照组(A组)、肝炎组(B组)及肝硬化并发肝癌组(C组)的HA、ⅢC、ⅣC及LN和AFP的含量,用WesternBlotting检测肝癌手术的癌组织、癌旁组织AFP、DR5和DcR1的表达。结果 HA、LN、ⅢC、ⅣC和AFP的血清含量由高到低:C组>B组>A组;(1)ⅢC、ⅣC、LN的相关性:A、B、C组ⅢC、ⅣC、LN表达呈正相关,r分别为0.623、0.651、0.714(P均<0.05)。(2)C组的各个观察指标均高于B组和A组,特别是血清AFP和HA含量,在A组和B组之间尽管也有统计学的意义(P<0.05),但是C和A、B组比较,这两者的含量显著性升高(P<0.001)。(3)WesternBlotting分析显示,癌旁组织的AFP和DcR1表达明显低于癌组织(P均<0.05);而DR5在癌旁组织表达则明显高于癌组织(P均<0.05)。结论由肝炎到肝硬化、肝癌的过程中HA的累聚以及LN、ⅢC、ⅣC和AFP的表达是一个渐进的基因激活过程;AFP、DR5和DcR1在肝癌组织的表达变化预示癌细胞耐受凋亡诱导。

Objective To study the change of hyaluronic acid（HA）,laminin（LN）,collagen Ⅲ（ⅢC）,collagen Ⅳ（ⅣC）,alpha fetoprotein（AFP）,tumor necrosis factor-related apoptosis inducing-ligand（TRAIL）receptor-2（DR5）and decoy receptor-1（DcR1）in the serum correlated with the development of hepatic fibrosis or primary hepatic carcinoma.Methods The serous concentration of HA,LN,ⅢC,ⅣC and AFP in normal control（A group）,hepatitis group（B group）and hepatic cirrhosis or primary hepatic carcinoma group（C group）were detected by ELISA;The expression of AFP,DR5 and DcR1 in lateral cancer or hepatoma tissue were analyzed by Western Blotting.Results The concentration change of HA,LN,ⅢC,ⅣC and AFP were found significantly higher in 52 patients than those of the normal controls or hepatitis group.The levels of AFP and LN in serum is no significant difference in A group between B group,but C group was significant higher than A and B groups（P0.01）;The expression of AFP,DR5 and DcR1 in primary hepatic carcinoma were significantly higher than lateral cancer（P0.05）.Conclusions The accumulation of HA and transactivation of LN,ⅢC,ⅣC and AFP genes were predictors in the development of the hepatoma;The expressed alteration of AFP,DR5 and DcR1 were a critical mechanism for hepatoma cells against the apoptosis induced by TRAIL.