SHH信号途径相关蛋白在结肠肿瘤组织中过度表达与STAT3活化的关系

Overexpression of sonic hedgehog pathway molecules and STAT3 activation in colonic tumors

目的:探讨SHH途径相关蛋白在结肠良恶性肿瘤中的表达情况及与STAT3活化之间的关系.方法:免疫组织化学检测20例正常结肠组织、42例结肠腺瘤以及77例结肠腺癌组织中SHH、GLI1、PTCH1、HHIP和磷酸化STAT3(P-STAT3)的表达,并评价他们之间及其与临床病理因素的关系.结果:相比正常结肠组织,SHH、GLI1、PTCH1和HHIP在结肠腺瘤及腺癌中均过度表达(95.2%,75.3%vs0.0%,P<0.05;66.7%,84.4%vs0.0%,P<0.05;23.8%,58.4%vs0.0%P<0.05;42.9%,36.4%vs25.0%),且在腺癌组织中SHH和GLI1的表达与肿瘤的病理分级有关(P<0.05).SHH及GLI1之间的表达有显著相关性(r=0.498,P<0.01),而腺癌组织中STAT3的活化(P-STAT3的表达)与SHH及GLI1的表达关系密切(r=0.525,P<0.01;r=0.637P<0.01).结论:SHH信号途径与结肠肿瘤的发生及进展有一定的关系,该途径的关键信号蛋白在结肠腺癌中的过度表达可能与STAT3信号途径的活化有协同作用.

AIM：To determine the expression pattern of sonic hedgehog（SHH） signaling pathway molecules and analyze their relationship with STAT3 activation in colonic tumors.METHODS：Paraffin-embedded tissue sections of 20 normal colon tissue specimens,42 colonic adenoma specimens,and 77 colonic adenoma adenocarcinoma specimens were used in the study.The expression of SHH,GLI1,PTCH1,HHIP and P-STAT3 in these specimens was detected by immunohistochemistry.The correlation of the expression of HH molecules with clinicopathological parameters and P-STAT3 expression was then evaluated.RESULTS：All the SHH signaling pathway molecules examined were overexpressed in colonic adenomas and adenocarcinomas when compared with normal colon tissue（95.2% and 75.3% vs 0.0%,both P〈0.05;66.7% and 84.4% vs 0.0%,both P〈0.05;23.8% and 58.4% vs 0.0%,both P〈0.05;42.9% and 36.4% vs 25.0%,both P〈0.05）.SHH and GLI1 expression was correlated with tumor grade（both P〈0.05）.There was a significant correlation between SHH and GLI1 expression in colonic adenomas and adenocarcinomas（r = 0.498,P〈 0.01）.Overexpression of activated STAT3（P-STAT3） was significantly correlated with SHH and GLI1 expression in colonic adenocarcinomas（r = 0.525,P 〈0.01;r = 0,637,P 〈0.01）.CONCLUSION：SHH signaling pathway may play a role in the progression of colonic tumors.The finding that SHH overexpression is correlated with STAT3 activation in colonic tumors indicates that there may be a synergetic effect between the two signaling pathways.