RhoA/ROCK信号通路在胃癌中的表达及其与胃癌生物学行为的关系

Relationship between expression of RhoA/ROCK signaling pathway and biologic behaviors of gastric carcinoma

目的检测人胃癌组织中RhoA、ROCK-Ⅰ、PI3K、HIF-1α及血清血管内皮生长因子(vascular endothelial growth factor,VEGF)表达,了解RhoA/ROCK信号通路在胃癌发病过程中是否活化及其与胃癌新生血管形成、临床病理分期之间的关系。方法选取广东省人民医院2010年10月-2012年10月行手术切除癌组织的胃癌患者60例,收集手术切除的胃癌组织60份和距癌边缘>10 cm的正常胃组织60份,并留取前述60例胃癌患者及本院同期胃镜检查正常的20名健康人群血清标本。应用免疫组化及Western blotting检测胃癌组织及癌旁正常组织中RhoA、ROCK-Ⅰ、PI3K、HIF-1α蛋白表达,ELISA法检测胃癌组及正常对照组血清VEGF水平,分析各指标与胃癌分化程度、肿瘤大小、淋巴结转移、远处转移、浸润深度和临床分期及患者性别、年龄之间的关系。结果胃癌组织中RhoA、ROCK-Ⅰ、PI3K、HIF-1α表达水平高于癌旁正常组织(P<0.05),胃癌组血清VEGF水平明显高于对照组(P<0.05)。胃癌组织中RhoA、ROCK-Ⅰ、PI3K、HIF-1α表达量及血清VEGF水平与患者性别、年龄、肿瘤大小及分化程度无关,而与胃癌的TNM分期、侵犯浆膜、淋巴结转移及远处转移相关(P<0.05)。结论 RhoA、ROCK-Ⅰ在胃癌中高表达,其可能通过激活PI3K/Akt/m TOR信号转导通路上调HIF-1α、VEGF表达而影响胃癌的发生、发展、侵袭和转移,为临床发现胃癌的治疗新靶点提供了参考依据。

Objective To detect the expressions of RhoA, ROCK- I , PI3K, HIF-1α in human gastric carcinoma and the level of serum vascular endothelial growth factor （VEGF） , then explore the relationship between these biomarkers and clinicopathological characteristics. Methods From Oct. 2010 to Oct. 2012 in Guangdong General Hospital, 60 cases of pathologically confirmed gastric cancer after surgical treatment were enrolled, gastric cancer tissues and adjacent normal tissues （over 10 cm from cancer tissues） were collected. Immunochemical stain （IHC） and Western blotting were used to detect the expressions of RhoA, ROCK- I , PI3K, HIF-1α in the tissues. The serum samples of 60 gastric cancer patients and 20 healthy controls were collected and enzyme-linked immunosorbent assay （ELISA） was used to assess the serum level of VEGF. The correlations between the expressions of these biomarkers and the clinicopathological parameters including tumor differentiation grade, size, lymph node metastasis, distant metastasis, depth of invasion, TNM stage, gender and age were analyzed. Results Expressions of RhoA, ROCK- I , PI3K, I-IIF-IoL in gastric carcinoma were significantly higher than those in adjacent normal gastric tissues and serum VEGF was highly expressed in gastric cancer patients than healthy controls （P 〈0.05）. Expressions of RhoA, ROCK-] , PI3K, HIF-1α in gastric carcinoma and serum VEGF were related with TNM stage, serosal invasion, lymph node metastasis and distant metastasis （P 〈 0.05） , but not correlated with the gender, age, tumor size and differentiation grade. Conclusion RhoA and ROCK- I are highly expressed in gastric carcinoma, and may increase the expressions of HIF-lot and VEGF by activating the PI3K/Akt/mTOR signaling pathway and then influence the occurrence, development, invasion and metastasis of gastric cancer. This may be a potential therapeutic target in gastric cancer treatment.