Detection And Analysis Of Mediastinal Lymph Node Metastasis Associated Genes Of Lung Adenocarcinoma In Patients With EGFR Sensitive Mutation

Background:In recent years,the diagnosis and treatment of lung cancer has made great progress,but the total survival rate of 5 years after surgery is still less than 50%.Non-small cell lung cancer(NSCLC)accounts for 80% in lung cancer.Accurate staging for patients with NSCLC not only helps to formulate reasonable treatment,can also evaluate prognosis.Current lung cancer staging system is an international TNM staging,and the key to the TNM staging of lung cancer and the challenge is for the judgment of the status of the mediastinal lymph nodes(MLN).The value of positron emission tomography(PET)has become an increasingly important in the clinical application for lung cancer,for diagnosis,TNM staging of lung primary tumors,evaluating the response to treatment and prognosis of patients and so on,Especially,PET can guide sketching radiotherapy target for the radical postoperative.However,PET cannot provide accurate anatomic localization,PET/CT can perfectly combine the biological information of PET and the anatomic information of CT.The sensitivity and accuracy of PET/CT is greatly increased,but it still has false positives and false negatives.Recent studies have shown that differentially expressed genes of microarray can be used as a predictor for patients with MLN.Therefore,the first part of this study was to explore the value of PET/CT and contrast enhanced CT in diagnostic of MLN metastasis in lung cancer;The second part was to use the next generation sequencing(NGS),high content screening(HCS)to screen the key MLN-associated genes in lung cancer.Research purposes:1.Compare the preoperative imaging examination of PET/CT and contrast enhanced CT chest with the postoperative pathologic results of the status of MLN of patients with lung cancer to explore the value of PET/CT and contrast enhanced CT examination in the diagnosis of MLN in lung cancer.2.Use the transcriptome sequencing and high content screening to screen the MLN metastase-related genes.Research methods:1.To collect 243 pairs of mediastinal lymph nodes with postoperative pathologic results of 94 cases lung cancer patients diagnosed by pathological detection and preoperative adept PET/CT and chest 64 contrast enhanced CT examin ation among half a month,record the status of mediastinal lymph nodes,respectively.The positive diagnostic criteria for PET/CT isSUVmax acuity 2.5,and the criteria of the contrast enhanced CT is the short diameter of the lymph nodes is10 mm or longer or exist the liquefaction necrosis.Data statistics using SPSS12.0 software.2.Transcriptome expression profile of patients with and without MLN metastasis was detected in clinical specimens of lung adenocarcinoma with sensitive EGFR mutations,extracted differentially expressed genes(DEGs)by biologic analysis;For up-regulated expression of DEGs,we next step used the HCS to screen MLN metastasis-related genes.The results of the research 1.The the accuracy(ACC),sensitivity(SEN),specificity(SPC)and positive predictive value(PPV)and negative predictive value(NPV)of contrast enhanced CT and PET/CT in the diagnosis of MLN metastasis in lung cancer is 80.7% vs 67.5%P=0.001,79.5% vs 60.3%P=0.009,81.2% vs 70.9%P=0.028,66.7% vs 49.5%,P=0.017,89.3% vs79.1%,P=0.015,respectively.2.According to pathology status,64 cases were rectified which diagnosed differently by contrast enhanced CT and PET/CT,among which 48 cases were correctly diagnosed by contrast enhanced CT at first while the other 16 cases were correctly diagnosed by PET/CT.After correction,the accuracy,sensitivity,specificity,positive and negative predict value for diagnosing mediastinal lymph node by both methods were 87.2%,85.9%,87.9%,77.0% and 92.9%,respectively.3.The diagnostic accuracy,sensitivityand specificity of conjunction showed a distinguishing increasing than PET/CT alone,while no significantly difference compared with contrast enhanced CT alone.4.Five genes(ZNF296,N6AMT1,TBCC,DDX49 and BCDIN3D)may influence the growth of the PC-9 cells.5.Nine genes(BDH1,DCXR,DDX49,GTF2H5,HYLS1,ISYNA1,TAF8,BCDIN3 D and MIA3)may be involved in process of transfer of the PC-9 cells.Conclusion:1.Contrast enhanced chest CT was better in diagnosis of mediastinal lymph node metastasis than PET/CT among lung cancer patients.Combination of the contrast enhanced chest CT and PET/CT may improve the diagnosis of mediastinal lymph node metastasis among lung cancer patients.2.Five genes(ZNF296,N6AMT1,TBCC,DDX49 and BCDIN3D)may influence the growth of the lung adenocacinoma.Nine genes(BDH1,DCXR,DDX49,GTF2H5,HYLS1,ISYNA1,TAF8,BCDIN3 D and MIA3)may be involved in process of MLN matastasis of lung adenocacinoma.