The Expression And Clinical Sigificance Of MTOR,elF4E In Lung Squamous Cell Cancer

Background and ObjectiveAt the beginning of 20th century lung cancer was still a rare disease, as the growth of human life span,smoking population,industry pollutions and so on,the morbidity and mortality of lung cancer started to grow rapidly worldwide at the middle of 20th century. World Health Organization reports that lung cancer and AIDS will be two kind of diseases that will do severe harm to human health in the 21th century. Data that is made public by China Ministry Of Health in May 2008 show that lung cancer is the leading cause of the mortality of all kinds of malignant tumors among both male and female patients.According to the pathology and clinical features, lung cancer can be devided into small cell lung cancer(SCLC) and non-small cell lung cancer(NSCLC), of which NSCLC makes up 80-85%. Comprehensive treatment is adopted, of which operations are the most important.50%-70% cases after operations prove to be squamous cell carcinoma of the lung, operation is the main method,but the 5 year survival rate(SR) is 20%-50%.As the devolopment of research into neoplasia molecular biology features, the relationship between the weakness and abnormal activation of the cellular signal transduction system and the neoplasia,growth,as well as prognosis has already been paid the most attention, and interference of the cellular signal transduction system as a method to treat tumors opens a new era as biologic therapy. Mammalian target of rapamycin(mTOR) signal transduction pathway is newly discovered that is in the center signal transduction pathway. mTOR signal pathway plays the most important part in growth regulating, in many physiologic and pathologic processes, such as the growth, differentiation, multiplication, migration of cells, which is focused by the tumors specialists at present, which proves to be true in the research of breast cancer, lung cancer, glioma and so forth. Molecular targeted therapy for neoplasm specificity is gradually paid much attention by people.Mammalian target of rapamycin(mTOR) is a kind of highly conserative atypical Ser/Thr protein kinase, which belongs to phosphatidylinositol kinase-related protein kinase(PIKK) family, MW289 kDa,contain 2,549 amino acid. Activiated by upper factors such as growth factor, insulin, nutrient factor, pressure and so on, mTOR brings about phosphorylation of promoting factor 4E binding protein 1(4EBP1) in eukaryotic cell, and lead to the release of 4EBP1 from eukaryotic translation initiation factor 4E(elF4E),which lies in the 5'cap of the mRNA, while eIF4E,eIF4G,eIF4B,eIF4A are conbined into eIF4F.Because of the high expression of eIF4E, The activity of CYCD1,Rb protein, HIF1,VEGF,ornithine decarboxylase(ODC) (a kind of regulating fator in the untranslated region(UTR) in the 5'end of the mRNA) improves, thus it enhances the translation of the mRNA, turns cells from G1 period to S period, regulates the growth and metabolism of the cells. In this thesis the anthor uses immunohistochemistry(IHC) method to do researh on mTOR in the tissue of hunman lung cancer and the expression of eIF4E in downstream, then anylize the relationship between their expressions and the clinical parameter, in order to provide theory evidence for molecular targeted therapy of squamous cell carcinoma of the lung.Materials and Methods80 cases surgical removed that prove to be squamous cell carcinoma of the lung by pathologic evidence with complete materials was chosen,while each case contains cancer focus and lymph nodes,and 10 cases tissue around the tumors and 10 cases of normal lung tissue makes up control group.which consisted of 64 men and 16 femen.The patients age range from 36 to 75 years, the average age is 59.4±9.1 years. IHC SP method is adopted,PBS fluid instead for anti-negative contrast.Known tumor markers for positive contrast,while comparision in the same group.Double-blind method is adoptedand two doctors from patholody department will judge the result by scoring.SPSS15.0 version statistics software is applied to deliverχ2 test and Fisher accurate test and Spearman related analysis.Significance level a=0.050.Results1. mTOR and eIF4E are located in the cytoplasm,part of them lies in the cell membrane,positive staining is light yellow,brown madder or brown color.2.mTOR and eIF4E expression rate are 52.5% and 75%,both obviously higher than the control group(P<0.05),which is no difference in tissue around tumor and normal lung tissue.3.mTOR and eIF4E in squamous cell carcinoma is apparently related with the differentiation grade of the tumor,size of the tumor,lymph node metastasis.The relationship between the expression of mTOR and eIF4E and clinical stages are as follows:no significance betweenⅠa andⅠb,Ⅱa andⅡb, stageⅠand stageⅡas well as stageⅡand stageⅢa (P>0.05),obvious significance of stageⅠstageⅢa (P<0.05),it has nothing to do with the number of lymph node metastasis.The gender,age,whether smoking or not of the patients is independent.4.Spearman correlation test show that mTOR and eIF4E in squamous cell carcinoma of the lung is significantly positive correlated(r=0.376,p=0.001).conclusionsThe expression of mTOR and eIF4E in squamous cell carcinoma increases more significantly than the tissue around the cancer focus and normal lung tissue.mTOR and eIF4E may play a role in the occurance and development of the squamous cell carcinoma of the lung.The result of this research provides theory evidence for molecular targeted therapy of squamous cell carcinoma of the lung.