RhoC及其调节因子RhoGDIa在非小细胞肺癌中的表达及临床意义

Expression and clinical significance of RhoC and RhoGDIa in non-small cell lung cancer

背景与目的RhoC在许多癌组织中过表达,而且与肿瘤的转移密切相关。RhoGDIα(Rho GDP dissociation inhibitor)被认为是Rho的负性调节因子,但目前其在肿瘤中的研究有限,而且在不同肿瘤中结果不一。本研究旨在探讨RhoC及其调节因子RhoGDIa在非小细胞肺癌的表达、二者间的关系及临床意义。方法应用免疫组织化学、Western blot、RT-PCR分别检测100例石蜡包埋肺癌组织、60例新鲜肺癌组织、正常支气管上皮细胞、肺癌细胞系中RhoC、RhoGDIa蛋白和mRNA的表达;分析其与临床病理参数间的关系。结果RhoC、RhoGDIa蛋白和mRNA在非小细胞肺癌组织和肺癌细胞系中的表达均明显高于相应的正常肺组织及正常支气管上皮细胞。在肺巨细胞癌高侵袭转移能力亚型BE1中,RhoC和RhoGDIa表达高于低侵袭转移能力亚型LH7。RhoC和RhoGDIa表达与淋巴结转移和临床分期有关。RhoC、RhoGDIα的过表达与患者的生存率低相关,在一定程度上提示患者的不良预后。RhoC的表达与RhoGDIα的表达正相关。结论RhoC、RhoGDIa可能参与肺癌的发生、发展。二者的表达与肺癌细胞的转移相关,可分别作为影响肺癌预后的独立风险因素。

Background and objective RhoC is known to be overexpressed in cancer and to regulate motility of cancer cells. The activities of RhoC axe negatively regulated by guanine nucleotide dissociation inhibitor a （GDIa）, but the knowledge of its role in cancer is quite limited and the results axe controversy in different cancers. The purpose of the present study is to investigate the expression of RhoC and RhoGDI α and analyze the correlation between RhoC and RhoGDI α expression and clinicopathological factors. Methods The expression patterns of RhoC and RhoGDI α were examined by immunohistochemistry in 100 non-small cell lung cancers （NSCLC）. Results The expression levels of RhoC and RhoGDI α proteins and mRNA were significantly enhanced in all tumor samples than those in normal tissues originating from the same individual. There was an elevated expression of RhoC and RhoGDIa protein and mRNA in subclone of lung giant cell carcinoma cell line with a higher metastatic capacity BE1 than in LH7 with a lower metastatic capacity. Both the overexpressions axe regulated on the mRNA level. Elevated levels of RhoC and RhoGDI α in lung cancer tissues were correlated with the nodal involvement and clinic TNM stage. The overexpression of RhoC and RhoGDIa is correlated with the lower survival duration of the patients. And RhoC expression was positively correlated with RhoGDIa. Conclusion RhoC and RhoGDI α may play roles in lung cancer, and correlated with metastasis of lung cancer, they may be independent factors of NSCLC prognosis.