The Expression And Relationship Of HIF-1αand Ki-67with Radiotherapy In Non-small Cell Lung Cancer

Background:Lung cancer is the most malignancy in morbidity andmortality now,non-small cell lung cancer(NSCLC)accounts for approximately80%of all cases of lung cancer.Over65%-75%of patients receiving differentlevels of radiotherapy.Although radiotherapy equipment and technologyimprovement has been improved to some extent, the rate of local recurrenceand5years survival is not satisfactory.It is found that tumor cell is associatedwith radiosensitivity.With the cell radiosensitivity and its influencing factorunderstanding, the four main factors of radiation sensitivity effects such asinherent sensitivity of tumor cells,hypoxic cell,hypoxia clonal cell proportionof tumor and radiation damage repair are increasely explored.Among them,theeffect of oxygen and hypoxia cell reoxygenation has become a hotspot incurrent research,and hypoxia inducible factor-1(HIF-1) pathway is a importantway in oxygen effect.Hypoxia inducible factor-1α (HIF-1α),which plays aimportant role in hypoxia microenviroment,is a poor prognosis factors forhumor patients. Tumor proliferation factor(Ki-67),relative with the tumoroccurrence, development,invasion and metastasis,recurrence and prognosis,isassociated with proliferating cell nuclear antigen.Objective:This study was to explore the protein expression of HIF-1α andKi-67in non-small cell lung cancer using immunohistochemical method(immunohi-stochemistry,IHC),and research the relationship betweenHIF-1α and Ki-67and clinical pathological features and prognosis ofNSCLC.The aim of the study is to provide more theoretical basis and newstrategies and approaches for the individual treatment,which is expected to oneof the important targets for gene therapy.Methods:166cases of NSCLC patients without operation,KPS≥70,were collected from December2008to December2010in the oncology department of HebeiGeneral Hospital.These patients were treated with chemoradiotherapy.Clinical datas were completed.All the patients were diagnosed by biopsyingwith fiberbronchoscopy or percutaneous lung biopsy.There were42male and24female,mean age of61.95±12.45years,medial age of65.5years.2The protein expression of HIF-1α and Ki-67in66cases of NSCLC weredetected with immunohistochemistry(SP method).The relation betweenHIF-1α and Ki-67protein expression with clinical-pathological parametersand prognostic of NSCLC were analyzed.3The data was analyzed using SPSS13.0.According statistical data ofdifferent respectively by means of χ2test, Spearman rank correlationanalysis and Kaplan-Meier survival analysis,P<0.05with statisticaldifference.Results:1Expression of HIF-1α in NSCLC:The protein expression of HIF-1α was observed in tissue of NSCLC, andthe protein mainly expressed in cell nuclei. Brown yellow,dispersion or focaldistribution, the positive expression rate was56.1%(37/66).The results showedthat the positive expression of HIF-1α was significantly correlated with TNMstage(r=0.333,P=0.016)and lymph node metastasis(r=0.276,P=0.020).Whilethere was no significance with gender, age, pathology type of tumor and tumordegree of differentiation (P>0.05).2Expression of Ki-67in NSCLC:The positive expression of Ki-67protein mainly was observed in cellnuclei,brown yellow particles,the positive rate was62.1%(41/66).It is showedthat the positive expression of Ki-67was significantly correlated with TNMstage(r=0.314,P=0.027),lymph node metastasis(r=0.338,P=0.004)and tumordegree of differentiation(r=0.321, P=0.023).While there was no significancewith gender, ageand and pathology type of tumor (P>0.05).3The relationship between expression of HIF-1α and Ki-67:The co-expression of HIF-1α and Ki-67was28cases and there was a close correlation between them in the non-small cell lung cancer tissues(r=0.301, P=0.01).4The relationship between expression of HIF-1α and Ki-67and radio ther-apy effect:In66cases,The remission rate of radiotherapy,the1-,2-and3-year survivalrate of the patients with positive and negative expression of HIF-1a was21.6%,56.8%,13.5%,0.0%and78.4%,90.9%,54.5%,32.7%,respectively.Theremission rate of radiotherapy,the1-,2-and3-year survival rate of the patientswith positive and negative expression of Ki-67was61.0%,58.1%,14.0%,0.0%and28.0%,80.0%,66.7%,33.3%,respectively.With Kaplan-Meiersurvival curve analysis,the expression of HIF-1α was negatively correlatedwith survival.The survival rate in radiation response rate and survival rate thepositive expression of HIF-1α was significantly lower than negative expre-ssion(P<0.05).The expression of Ki-67was positively correlated with radia-tion response rate,While negatively with survival.The radiotherapy responsewas higher than negative expression,while lower in survival(P<0.05).Conclusion:1HIF-1α and Ki-67had high expression in non-small cell lung cancer tis-sues,positively correlation with each other.2The remission rate,the1-,2-and3-year survival rate of the patients withpositive expression of HIF-1α were lower than negative.The remission rate ofradiotherapy with positive expression of Ki-67was higher than negative,but1-,2-and3-year survival rate was lower than negative.3The expression of Ki-67was relative TNM stage,lymph nodes meta-stasis and pathology type of tumor.The expression of HIF-1α was positivelyassociated with TNM stage,lymph nodes metastasis,radiation response andsurvival rate, and HIF-1α was used as the index of effect of radiotherapy.