CAJ | 학술논문

目的：探讨p21活化激酶4（ PAK4）在人非小细胞肺癌细胞系及人非小细胞肺癌组织中的表达及其临床意义。方法：采用Western blot及实时荧光定量PCR检测人支气管上皮（ HBE ）细胞、非小细胞肺癌细胞（ A549、NCI－H520、NCI－H460和NCI－H596细胞）、20例新鲜非小细胞肺癌组织及相应的癌旁组织中PAK4的表达情况；采用免疫组化检测210例非小细胞肺癌组织PAK4的表达情况；采用Kaplan－Meier法评估非小细胞肺癌患者术后5年生存率；用Cox比例风险模型分析PAK4对患者预后的影响。结果：非小细胞肺癌细胞（ A549、NCI－H520、NCI－H460和NCI－H596细胞） PAK4蛋白及mRNA表达均显著高于HBE细胞（ P＜0．05）；20例非小细胞肺癌组织中PAK4蛋白及mRNA表达高于癌旁组织PAK4蛋白及mRNA表达（ P＜0．05）；10例转移性非小细胞肺癌组织PAK4 mRNA表达显著高于10例原发性非小细胞肺癌组织（ P＜0．05）；免疫组化染色结果示210例非小细胞肺癌PAK4评分显著高于对应的癌旁组织。临床资料分析显示PAK4蛋白表达与非小细胞肺癌的分化程度、淋巴结转移、远处转移及临床分期有关（P＜0．05）；PAK4高表达组患者5年生存率显著低于PAK4蛋白低表达组患者（log－rank检验，P＜0．05），PAK4蛋白表达是非小细胞肺癌患者的独立预后因素。结论： PAK4蛋白高表达是非小细胞肺癌患者死亡的独立危险因素。
목적：탐토p21활화격매4（ PAK4）재인비소세포폐암세포계급인비소세포폐암조직중적표체급기림상의의。방법：채용Western blot급실시형광정량PCR검측인지기관상피（ HBE ）세포、비소세포폐암세포（ A549、NCI－H520、NCI－H460화NCI－H596세포）、20례신선비소세포폐암조직급상응적암방조직중PAK4적표체정황；채용면역조화검측210례비소세포폐암조직PAK4적표체정황；채용Kaplan－Meier법평고비소세포폐암환자술후5년생존솔；용Cox비례풍험모형분석PAK4대환자예후적영향。결과：비소세포폐암세포（ A549、NCI－H520、NCI－H460화NCI－H596세포） PAK4단백급mRNA표체균현저고우HBE세포（ P＜0．05）；20례비소세포폐암조직중PAK4단백급mRNA표체고우암방조직PAK4단백급mRNA표체（ P＜0．05）；10례전이성비소세포폐암조직PAK4 mRNA표체현저고우10례원발성비소세포폐암조직（ P＜0．05）；면역조화염색결과시210례비소세포폐암PAK4평분현저고우대응적암방조직。림상자료분석현시PAK4단백표체여비소세포폐암적분화정도、림파결전이、원처전이급림상분기유관（P＜0．05）；PAK4고표체조환자5년생존솔현저저우PAK4단백저표체조환자（log－rank검험，P＜0．05），PAK4단백표체시비소세포폐암환자적독립예후인소。결론： PAK4단백고표체시비소세포폐암환자사망적독립위험인소。
AIM:To investigate the expression and clinical significance of PAK4 in the cell lines and tissues of non-small cell lung cancer (NSCLC).METHODS:PAK4 expression in human bronchial epithelial (HBE) cells, NSCLC cell lines, NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR and Western blot.Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression.RE-SULTS:PAK4 was over-expressed in the NSCLC cell lines at both mRNA and protein levels compared with HBE cells ( P<0.05).PAK4 was over-expressed in the NSCLC tissues at both mRNA and protein levels compared with adjacent non-tumor tissues (P<0.05).PAK4 was over-expressed in the metastatic NSCLC tissues compared with the primary NSCLC tissues (P<0.05).Higher PAK4 staining scores were positively correlated with differentiation, lymph node metastasis, distant metastasis, and clinical stage.Kaplan-Meier analysis and log-rank test showed that overall survival was significantly different between the patients with up-regulated PAK4 and the patients with down-regulated PAK4 ( P<0.05) .PAK4 over-expression was associated with NSCLC progression.CONCLUSION:Increased PAK4 expression was associated with tumor invasion, metastasis and prognosis in the patients with NSCLC.PAK4 is an important prognostic marker and potential ther-apeutic target in NSCLC.