1.Changes And Prognostic Value Of Peripheral Blood TCR Repertoire Before And After Treatment In Patients With Advanced Lung Cancer 2.Genomic Characteristics Of Airway Epithelium In Different Parts Of Non-Smoking Lung Adenocarcinoma

Part ? Changes and prognostic value of peripheral blood TCR repertoire before and after treatment in patients with advanced lung cancerBackground:The immune status of patients with advanced lung cancer is closely related to their clinical outcomes,and the adaptive immune status is a key influencing factor of antitumor therapy.An indicator for systemic evaluation of the adaptive immune status is lacking.Peripheral blood is important in antitumour immunity,and the T-cell receptor(TCR)repertoire diversity is key for effective immunity.Objective:This study aimed to investigate changes in the adaptive immune status and the circulating T cell receptor ? chain(TCRB)diversity during the first few(1-4)treatment cycles and its clinical value in patients with advanced lung cancer.Materials and methods:TCRB-enriched sequencing data combined with transcriptomic RNA sequencing data of peripheral blood leukocytes were obtained from 72 patients with advanced lung cancer before and after targeted therapy or chemotherapy.Changes in the peripheral blood TCR repertoire during treatment and the relationship of the baseline circulating TCRB diversity with prognosis and therapeutic effects were evaluated.Results:We found that targeted therapy or chemotherapy did not significantly affect the T lymphocyte composition or circulating TCRB diversity(3.83 vs 3.74,t-test,p=0.16)in patients with advanced lung adenocarcinoma(LUAD)during the first few treatment cycles,which had little effect on the immune system.The first few cycles of chemotherapy have certain toxic and side effects on patients with advanced lung squamous cell carcinoma(LUSC)and small cell lung cancer(SCLC),but also promote the restart of the immune clearance process.Chemotherapy has little impact on the immune system of these two groups of patients.The higher circulating TCRB diversity was linked to improved therapeutic effects(t-test,p=0.00083)in LUAD patients receiving targeted therapy.Higher baseline circulating TCRB diversity was associated with better prognosis.In addition,a five-factor prognostic risk score model was built for more accurate prognosis prediction for LUAD patients.Conclusion:The chemotherapeutic agents for advanced lung cancer do not significantly affect adaptive immune function over the first few treatment cycles.The circulating TCRB diversity reflects the adaptive immunological repertoire and might be a convenient indicator for evaluating the adaptive immune status and prognosis.Part ? Genomic characteristics of airway epithelium in different parts of non-smoking lung adenocarcinomaBackground:Lung cancer is still the leading cause of cancer-related death worldwide,and the incidence of lung cancer in non-smoking population is gradually increasing.There is an urgent need to further explore the molecular mechanism of the occurrence and development of non-smoking lung cancer patients,so as to contribute to the early detection and early diagnosis of lung cancer.Objective:The purpose of this study was to explore the differences and association between the genomic characteristics of normal airway epithelium and cancerous sites in patients with non-smoking lung adenocarcinoma,in order to provide some evidence and inspiration for the occurrence,development,early detection and diagnosis of non-smoking lung adenocarcinoma.Materials and methods:This study combined WES and WGS sequencing data of airway epithelium,bronchial epithelium and the lung adenocarcinoma cancerous parts in 3 cases of non-smoking lung adenocarcinoma patients.Genome characteristics were characterized from theses aspects:the overall overview of the mutated genes,the type of a single base substitution,SNV number change,cosmic change,drive gene mutation spectrum detection,co-occurrence mutated genes,mutated genes involved in biological pathways and copy number variation and the structure of the chromosome variation.Results:We found that there were somatic mutations in normal airway epithelium,and common SNV and driver gene mutations were existed in normal airway epithelium and the cancerous sites.Different combinations of mutated genes disrupt important signaling pathways in normal airway epithelium and the cancerous sites.Further,copy number variation and chromosomal structure variation were detected in normal airway epithelium,and their genome was in a relatively stable state.Conclusion:The mutation characteristics of normal airway epithelium and the cancerous parts has certain commonality and this phenomenon provided certain support for field cancerization of airway in non-smoking lung adenocarcinoma patients.However,normal airway epithelium of the genome are still in a relatively stable state,and accumulation of somatic mutations in the normal airway epithelium are not enough to lead to malignant phenotype transformation,which fundamentally different from the cancerous parts.