The Study Of The Expression Of Livin,Caspase-3 And Ki-67 In Non-small Cell Lung Cancer And The Association

Objective To investigate the expression of two isoforms of Livin(Livinαand Livinβ),an inhibitor of apoptosis protein(IAP)family member,in non-small cell lung cancer(NSCLC)and to analyze the relationship between Livin expression and biological features of NSCLC.Another aim is to analyze the relationship between Livin expression and the expression of Caspase-3 or Ki-67,to discuss initially the mechanism of action of Livin and the value in targeted therapy.Methods (1) 90 samples were obtained from 48 specimens of NSCLC,29 specimens of para-cancerous lung tissues and 13 of various benign lung disease. The samples of NSCLC were re-divided into the adenocarcinoma group(n=21),squamous carcinoma group(n=24)and megacell carcinoma group(n=3);Of all NSCLC samples ,6 specimens were well differentiated,29 were moderately differentiated,10 were poorly differentiated and 3 were undifferentiated;According to TNM classification ,there were 11 stageⅠcases,18 stageⅡcases,14 stageⅢcases and 5 stageⅣcases;Among all NSCLC samples,there were 34 patients with lymph node metasasis and 14 without that.(2)Livin mRNA were detected by reverse transcription polymerase chain reaction(RT-PCR).Livin protein,phosphatic Caspase-3 and Ki-67 expressions were detected by immunohistochemical SP staining of tissue microarray(TMA). Analysis was also made according to the clinical and pathologic datas.Results (1)The expression level of Livin mRNA was in accordance with the level of Livin protein.The positive rates of Livin expression were respectively 66.67%,6.90%and 0.00%(P<0.05)in NSCLC,para-cancerous and benign disease lung tissues. The expression of Livin was higher and specific in NSCLC tissues.(2) Both expressions of LivinαmRNA and LivinβmRNA could be dectected in most of NSCLC tissues.The expression level of Livin mRNA was in accordance with that of Livin protein.(3)In group of patients with lymph node metasasis,the expression level was higher than it in another group without metasasis(P<0.05).Livin expression had no significant relationship with sex,age,size of tumor,smoking history,pathologic type,cell differentiation and clinicl stage of NSCLC patient(sP>0.05).(4)The positive expression rate of Caspase-3 in NSCLC was much lower than that in para-cancerous and benign disease lung tissues(P<0.0125),which was statistically correlated with the differentiation level of NSCLC(P<0.05).Moreover ,a negative correlation between Livin and Caspase-3 was observed(r=-0.344,P=0.017).(5)In NSCLC group,the Ki-67 labeling index(LI) was significantly higher than that in para-carcerous and benign lesion groups(P<0.05).The expression of Ki-67 was associated with cell differetiation,lymph node metasasis and clinical stage.A positive correlation was found between the expression of Livin and Ki-67(r=0.602,P=0.000).Conclusion (1) Livin expression was specificly up-regulated in NSCLC.The two isoforms of Livin , Livinαand Livinβ,were expressed at the same time in most of NSCLC patients.The expression level of Livin mRNA was in accordance with that of Livin protein.(2) The overexpression of Livin suggested that Livin might play an important role in invasion and metastasis in NSCLC.(3)The role of Livin in apoptosis might depend on the activated Caspase-3. Livin also might have the function of regulating the karyogenetic division of cells and promoting cell proliferation,which made cells of NSCLC grow unconditionally.(4) Livin might serve as a new target for the therapy of NSCLC.