胃癌中NPR-A、P38MAPK及细胞骨架Tubulin-a的表达及意义

Expression and clinical significance of NPR-A,P38MAPK and cytoskeleton Tubulin-a in gastric carcinoma

目的通过研究胃癌中心房钠尿肽受体A(natriuretic peptide receptor-A,NPR-A)、分子量为38的丝裂原活化的蛋白激酶(P38MAPK)和细胞骨架微管蛋白a(Tubulin-a)的蛋白及基因表达,分析其与临床特征的关系及相关性,为研究胃癌的发生、发展机制提供新思路,为胃癌的靶向治疗提供潜在的治疗靶点。方法收集承德医学院附属医院2016年9月至2017年9月手术切除的胃癌组织41例,正常胃黏膜组织41例。应用SP免疫组织化学技术、Western blotting技术和QRT-PCR技术检测胃癌组织和正常胃组织中NPR-A、P38MAPK和Tubulin-a蛋白和mRNA的表达情况。结果胃癌组织中NPR-A蛋白和mRNA表达低于正常胃黏膜组织,胃癌组织中P38MAPK、Tubulin-a表达高于正常胃黏膜组织,NPR-A表达与侵袭深度、分化程度、淋巴结转移、TNM分期有关;P38MAPK、Tubulin-a表达与侵袭深度、淋巴结转移、TNM分期有关。胃癌组织中NPR-A与P38MAPK、Tubulin-a蛋白的表达呈负相关(r=-0.441,P<0.01;r=-0.354,P<0.01);NPR-A与P38MAPK、Tubulin-a mRNA在胃癌组织中的表达均呈负相关(r=-0.581,P<0.01;r=-0.579,P<0.01)。结论胃癌的侵袭和转移可能是通过NPR-A调控P38MAPK信号通路进而影响细胞骨架Tubulin-a来完成的,NPR-A有可能成为潜在的治疗胃癌作用靶点。

Objective To study the protein and gene expression of natriuretic peptide receptor A(NPR-A),mitogen-activated protein kinase(P38 MAPK)with a molecular weight of 38,and cytoskeleton microtubule protein A(Tubulin-a)in central atrial carcinoma of gastric cancer,and analyze its relationship and correlation with clinical characteristics and to provide a new idea to study the mechanism of gastric cancer development and to provide a potential therapeutic target for the targeted treatment of gastric cancer.Methods Totally 41 cases of gastric cancer tissues and 41 cases of normal gastric tissues 10 cm away from cancer edge in Affiliated Hospital of Chengde Medical College from September 2016 to September 2017 were collected.SP immunohistochemical technique,Western blotting and QRT-PCR technique were used to detect the expression of NPR-A,P38 MAPK and Tubulin-a protein and mRNA in gastric cancer tissues and normal gastric tissues.Results In gastric cancer tissues,protein and mRNA expression of NPR-A were obviously lower than those of normal gastric tissue(P<0.05),and the expression of P38 MAPK and Tubulin-a in gastric cancer tissue was higher than that of normal gastric mucosal tissue.NPR-A expression was related to invasion depth,differentiation degree,lymph node metastasis and TNM stage(both<0.05).The protein and mRNA expression of P38 MAPK and Tubulin-a were closely related to depth of invasion,lymph node metastasis and TNM stage(both<0.05).The expression of NPR-A and P38 MAPK and Tubulin-a protein in gastric cancer tissues was negatively correlated(r=-0.441,P<0.01;r=-0.354,P<0.01)and the mRNA expression of NPR-A was negatively related with that of P38 MAPK and Tubulin-a(r=-0.581,P<0.01;r=-0.579,P<0.01).Conclusions Invasion and metastasis of gastric cancer can be accomplished by NPRA regulating P38 MAPK signaling pathway and then affecting cytoskeleton Tubulin-a;NPR-A may become a potential target for the treatment of gastric cancer.