摘要
目的分析酸敏感离子通道1a(ASIC1a)及其介导的激活蛋白-1(AP-1)在肝细胞肝癌(HCC)组织中的表达,以及与患者临床特征的关系。方法在转录组水平,肝癌细胞中使用表达谱芯片和生物信息学分析ASICla干扰前后下游信号通路变化。进一步借助无锡市第三人民医院2010年1月至2014年12月收治的HCC患者临床病理资料,选取63例HCC组织,42例无瘤癌旁组织。应用免疫组化染色检测ASIC1a、c—Jun、c—Fos在组织中的表达。使用非参数Spearman秩相关分析三者之间的关系。结果基因芯片和生物信息分析筛选出AP-1(由c—Jun与c—Fos组成)。蛋白印迹(Weatern blot)检测ASIC1a干扰后,干扰组c-Jun和c-Fos蛋白表达水平明显低于对照组。在HCC组织中,ASIC1a、c-Jun与c—Fos阳性率高于癌旁组织,68.3%比19.0%,55.6%比11.9%,47.6%比11.7%,差异有统计学意义(P〈0.05)。相关分析显示,ASIC1a的表达与c—Jun、c-Fos的表达呈正相关(r=0.404、0.309,P〈0.05)。ASIC1a、c—Jun和c—Fos的表达与年龄、肿瘤直径大小、性别无关(P〉0.05),与肿瘤的临床分期、AFP值以及淋巴结转移有关(P〈0.05)。结论ASIC1a可能通过下游基因AP-1影响肝细胞肝癌的发生及发展。
Objective To investigate the expressions of acid sensing ion channel 1 a(ASIC1a) and activator protein-1 (AP-1) in hepatocellular carcinoma, and to analyze the relationship between expressions and clinical features. Methods At the transcription level, expression spectroscopy chips and bioinformatics were used to analyze the changes of signal pathways before and after ASIC1a interference in hepatoeellular carcinoma cells. 63 cases of HCC and 42 cases of tumor adjacent tissue samples were chosen from the Third People's Hospital of Wuxi, between January 2010 and December 2014. Immunohistoehemical staining was utilized to detect the expressions of ASIC1a, c-Jun, c-Fos. The relationships among the three were analyzed by the nonparametric Spearman rank correlation coefficient. Results After ASICla inhibition, the expression of AP-1 ( c-Jun and c-Fox) decreased significantly. The expressions of c-Jun and c-Fox were greatly decreased in interference group compared with control group. The positive rates of ASICla, c-Jun and c-Fos in HCC tissues were significantly higher than that of the adjacent tissues, 68. 3% vs. 19. 0%, 55. 6% vs. 11.9%, 47.6% vs. 11.7% (P 〈0.05). Correlation analysis showed that the expression of ASICla was positively correlated with c-Jun and c-Fos expression ( r = 0. 404, 0. 309, P 〈 0.05 ). The expressions of ASIC1a, c-Jun and c-Fos were not related to age, tumor diameter and gender ( P 〉 0. 05 ) , which were related to the clinical stage, AFP and lymph node metastasis of the tumor ( P 〈 0. 05 ). Conclusion ASIC1 a may affect the development of hepatocellular carcinoma through the downstream gene AP-1.
作者
金成
朱茂群
顾元龙
袁凤来
钱毅
高森
何友钊
Jin Cheng;Zhu Maoqun;Gu Yuanlong;Yuan Fenglai;Qian Yi;Gao Sen;He Youzhao(Department of Hepatobiliary Surgery, Wuxi Third People' Hospital affiliated to Nantong University, Wuxi 214041, China)
出处
《中华肝胆外科杂志》
CAS
CSCD
北大核心
2018年第6期376-380,共5页
Chinese Journal of Hepatobiliary Surgery
基金
国家自然科学基金(81301805)
江苏省卫计委项目(QNRC2016200)
江苏省333工程高层次人才项目(20161110615)
江苏省六个一工程项目(LGY2017012)
无锡市卫计委重大项目(Z201503)
关键词
肝细胞肝癌
酸敏感离子通道1α
激活蛋白-1
相关性
Hepatocellular carcinoma
Acid sensing ion channel 1α
Activator protein-l
Correlation