Raf激酶抑制蛋白在非小细胞肺癌中的表达及其临床意义

摘要

背景与目的 Raf激酶抑制蛋白( Raf kinase inhibitor protein,RKIP)属于磷脂酰乙醇胺结合蛋白家族的成员,RKIP参与ERK/MAPK、G蛋白偶联受体和NF-κB等信号传导过程,且RKIP的表达减弱或丢失与多种肿瘤的发生发展及侵润转移相关.本研究旨在探讨RKIP在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中的表达及其与NSCLC临床病理特征的相关性.方法 应用RT-PCR、Western blot及免疫组化方法检测83例NSCLC及其癌旁组织标本中RKIP的表达,并结合临床病理学资料进行统计学分析,所有病例均经病理诊断确诊,均无其它部位原发肿瘤,术前无化疗、放疗和免疫治疗史.结果 NSCLC中RKIP mRNA及蛋白的表达明显低于癌旁组织,差异有统计学意义(P＜0.05).RKIP与肿瘤分化程度、TNM分期、有无淋巴结转移及生存期有关(P＜0.05),但与患者的性别、吸烟、年龄及肿瘤的大小无关(P＞0.05).结论 RKIP的低表达与NSCLC的发生及侵袭转移有关,可作为NSCLC预测及预后评估的指标.%Background and objective Raf kinase inhibitory protein (RKIP) belongs to the phosphatidylethanol-amine binding protein family. RKIP is an endogenous inhibitor of the ERK/MAPK, NF-kB, and G protein-coupled receptor signaling pathways. This study aims to investigate the expression of RKIP in non-small cell lung cancer (NSCLC) and to determine the association of RKIP expression with the clinicopathologic features of NSCLC. Methods Reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry were used to detect RKIP expression in 83 specimens with NSCLC and normal lung tissues and to analyze the association of RKIP expression with the clinicopathologic features of NSCLC. All cases were confirmed by pathological diagnosis, and primary tumors were not found at other sites. No medical records of preoperative radiotherapy, chemotherapy, and immunotherapy were found in the groups. Results RKIP expression was down-regulated significantly in NSCLC compared with adjacent cancer tissues (P<0.05). It was associated with differentiation, pathological tumor-node-metastasis stage, survival time, and lympho invasion (P<0.05) but not with gender, smoking status, age, tumor size, and histologic type (P>0.05). Conclusion The deficiency of RKIP expression is positively correlated with carcinogenesis and invasion metastasis of NSCLC. RKIP is a potential marker and target for clinic therapy.