非小细胞肺癌中caspase-3、survivin和k-ras的表达及其意义

背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)的预后与众多因素有关,凋亡相关基因在肿瘤的发生发展过程中发挥重要的作用,但其在NSCLC中作为生物预后因素的意义还不明确。本研究的目的是探讨凋亡相关基因caspase-3、survivin、k-ras在NSCLC中的表达与不同临床病理特征和预后的关系,并探讨三者在NSCLC发生过程中可能存在的相关性。方法采用免疫组化SP二步法检测91例石蜡标本癌组织和癌旁正常组织中caspase-3、survivin、k-ras蛋白的阳性表达。结果Caspase-3在癌组织中阳性表达率低于癌旁正常组织,survivin、k-ras在癌组织阳性表达高于癌旁正常组织,均具有统计学差异(P<0.05)。Caspase-3阳性表达与年龄、病理类型、TNM分期、淋巴结状态、分化程度有关(P<0.05),而与病灶大小、有无吸烟史等无关(P>0.05);survivin阳性表达与年龄、TNM分期、分化程度、淋巴结状态有关(P<0.05),而与病理类型、病灶大小、有无吸烟史等无关(P>0.05);k-ras阳性表达与病理类型、吸烟有关(P<0.05),与年龄、TNM分期、淋巴结状态、分化程度、病灶大小等均无关(P>0.05)。Caspase-3与survivin的阳性表达呈负相关(r=-0.662,P<0.001)。Cox多因素分析survivin,caspase-3,TNM分期、病理类型、分化程度5个因素具有独立预后价值(P<0.05)。结论Survivin和k-ras在NSCLC中高表达,而caspase-3在NSCLC中低表达,可能在肿瘤细胞凋亡过程中起着重要的作用;Caspase-3低表达、survivin高表达可作为术后NSCLC预后不良的独立性因素;K-ras与NSCLC预后的关系需要进一步研究。

Expression and clinical significance of caspase-3、survivin and k-ras in non-small cell lung cancer

Background and objective The prognosis of non-small cell lung cancer (NSCLC) is related to many factors.Apoptosis-related genes play an important role in occurrence and development of tumors.The sig- nificance of apoptosis as a biological and prognostic factor has not been clearly established in NSCLC.The aim of the study is to evaluate the relationship between expression of caspase-3 ,survivin ,k-ras protein and the relationship between the expression of above proteins in NSCLC and theirs clinicopathological characteristics and prognostic sig- nificance and their potential relevance existing in NSCLC.Methods Caspase-3 ,survivin,k-ras protein expression were detected in NSCLC tissues and normal lung tissues adjacent to carcinomas Archival formalin fixed,paraffin embedded specimens from 91 patients who had undergone radical surgery by streptavidin-peroxidase immunohisto- chemistry.Results The positive rate of caspase-3 was significantly lower in NSCLC than in normal lung tissues adjacent to carcinomas;The positive rate of survivin,k-ras was significantly higher in NSCLC than in normal lung tissues adjacent to carcinomas(P<0.05).The positive rate of caspase-3 was related to the age,histological type, TNM stage,lymph node metastasia and differentiation(P<0.05),but not related to tumor size,smoke(P>0.05);the positive rate of survivin was related to the age,TNM stage ,lymph node metastasia and differentiation(P<0.05),but not related to histologic type ,tumor size,smoke(P>0.05);the positive rate of k-ras was related to the histologic type and smoke(P<0.05),but not related the age,TNM stage,lymph node metastasia,differentiation ,tumor size(P>0.05). Expression of easpase-3 was negatively correlated with survivin(r=-0.662,P<0.001).The multivariate analysis with Cox hazard model,survivin,caspase-3,histologic type,differentiation,TNM stage could be indicators for the prognosis of patients with NSCLC(P<0.05).Conclusion There are over-expressions of survivin,k-ras protein in NSCLC and both are significantly higher than those in the normal tissue.However,caspase-3 presents the reverse result;Higher expression of survivin,lower expression of caspase-3 might be the adverse prognostic index for sur- vival in resected NSCLC patients,which indicate they might act synergistically in apoptosis of NSCLC;the relation- ship between the expression of k-ras and the prognosis of NSCLC is still not clear.