肝细胞癌组织中GRP78和p-PERK蛋白的表达及其与临床病理特征的关系

Expressions of GRP78 and p-PERK in hepatocellular carcinoma and their relationships with clinicopathological features

目的观察人类肝细胞癌(HCC)组织中内质网应激(ERS)相关蛋白葡萄糖调节蛋白78(GRP78)和磷酸化蛋白激酶R样内质网激酶(p-PERK)蛋白的表达变化及其与临床病理特征的关系。方法收集手术切除的HCC组织(HCC组)及其癌旁组织(癌旁组)标本各40例,HCC组根据病理分化类型分为高(n=12)、中(n=15)及低分化组(n=13),收集HCC组患者的年龄、性别、术前甲胎蛋白(AFP)水平、肿瘤大小及病理分化类型等临床特征资料;采用免疫组织化学法检测2组标本GRP78和p-PERK的阳性定性表达,Western blot法检测GRP78和p-PERK蛋白的半定量表达,采用Pearson相关分析GRP78和p-PERK蛋白的表达与临床病理特征的关系。结果HCC组标本中GRP78和p-PERK蛋白的阳性染色呈现弥散分布的黄褐色颗粒,高、中、低分化组标本中GRP78和p-PERK蛋白的阳性表达均分别较癌旁组增高,且阳性表达与HCC分化程度有关(P<0.05);与癌旁组相比,高、中、低分化组中GRP78、p-PERK表达水平增高(P<0.05),且GRP78、p-PERK的蛋白表达水平和肿瘤的分化程度有关(P<0.05);GRP78阳性表达率与AFP水平、肝脏肿瘤大小有关,AFP高水平及肿瘤直径增大,表达率增高(P<0.05);随着肝癌的分化程度降低,GRP78、p-PERK蛋白的阳性表达率逐渐增高(P<0.05);GRP78和p-PERK蛋白表达之间呈正相关(r=0.482,P=0.012)。结论GRP78和p-PERK蛋白在HCC组织中的表达高于癌旁组织,且与HCC分化程度有关,该两项指标可望成为临床检测HCC及判断预后的肿瘤标志物。

Objective To observe the expressions of endoplasmic reticulum stress(ERS)related proteins glucose regulatory protein 78(GRP78)and phosphorylated protein kinase R-like endoplasmic reticulum kinase(p-PERK)in human hepatocellular carcinoma and their relationships with clinicopathological features.Methods Forty cases of hepatocellular carcinoma tissues(HCC Group)and forty cases of paracancerous tissues(Paracancerous Group)were collected,among which HCC Group was further divided into high(n=12),medium(n=15),and low differentiation groups(n=13)according to their pathology;the data of age,gender,AFP level,tumor size,and pathological differentiation degree of HCC group were collected.Immunohistochemistry was adopted to detect the positive qualitative expressions of GRP78 and p-PERK in each group;Western blot was adopted to detect the semi-quantitative expressions of GRP78 and p-PERK in each group;Pearson correlation was adopted to analyze the relationship between GRP78 and p-PERK protein expressions and clinical features.Results The positive stainings of GRP78 and p-PERK in HCC group showed diffuse yellow brown granules;the positive expressions of GRP78 and p-PERK in high,medium,and low differentiation groups were higher than those in paracancerous group,and the positive expression was related to the degree of HCC differentiation(P<0.05);compared with paracancerous group,the expression levels of GRP78 and p-PERK in high,medium and low differentiation groups were significantly higher(P<0.05),and the protein expression levels of GRP78 and p-PERK were related with tumor differentiation degree;GRP78 expression rate was related with AFP level and liver tumor size:GRP78 expression rate increased with high AFP level and increased tumor diameter(P<0.05);with the decrease of differentiation degree of liver cancer,the positive expression rates of GRP78 and p-PERK increased gradually(P<0.05),and there was a positive correlation between GRP78 and p-PERK protein expressions(r=0.482,P=0.012).Conclusion Expressions of GRP78 and p-PERK in HCC tissues are higher than those in paracancerous tissues,and are related with HCC differentiation degree,which may become a tumor marker for HCC clinical detection and prognosis.