1.Peripheral Blood Transcriptome Heterogeneity And Prognostic Value In Lung Cancer Patients Revealed By RNA-Seq 2.The Landscape Of Peripheral Immune System During Human Aging And Oncogenesis

Part One:Peripheral blood transcriptome heterogeneity and prognostic value in lung cancer patients revealed by RNA-Seq.Understanding of the complex interaction between the peripheral immune system and lung cancer(LC)remains incomplete,limiting patient benefit.Here,we aimed to characterize the host peripheral immune response to LC and investigate its potential prognostic value.Bulk RNA sequencing data of peripheral blood leukocytes(PBLs)from healthy volunteers and LC patients(n=142)were analyzed for characterization of host systemic immunity in LC.We observed broad blood transcriptome perturbations in LC patients that were heterogeneous,as two new subtypes were established independent of histology.Functionally,the heterogeneity between the two subtypes included dysregulation of diverse biological processes,such as the cell cycle,blood coagulation,and inflammatory signalling pathways,together with the abundance and activity of blood cells,particularly lymphocytes and neutrophils,ultimately manifesting as differences in antitumour immune status.Based on these findings,a prognostic model composed of ten genes dysregulated in one LC subtype with relatively poor immune status was developed and validated in a Gene Expression Omnibus(GEO)dataset(n=108),helping to generate a prognostic nomogram.Collectively,our study provides novel and comprehensive insight into the heterogeneity of the host peripheral immune response to LC.The expression heterogeneity-based predictive model may help guide prognostic management for LC patients.Part two:The landscape of peripheral immune system during human aging and oncogenesisAs a hallmark of the aging immune system,immunosenescence leads to higher cancer rates and increased susceptibility to infections in the aged population.On the other hand,cancer is considered to be a systemic disease that affects the host immune response ability to a certain extent.Understanding the characteristic changes of human immune system in aging and carcinogenesis will help to comprehend the relationship between carcinogenesis and aging.At present,a comprehensive and in-depth understanding of the human peripheral immune response to aging and cancer is still lacking.In this study,we used an aging cohort containing subjects with different ages and a cancer cohort containing colorectal cancer patients and healthy controls to explore the peripheral immune changes in aging and oncogenesis.We found that abnormal immune cell abundance,especially T lymphocytes,as well as cell senescence and functional exhaustion becomes prominent with increasing age.Age also contribute to underlying immune-inflammatory status and dysfunction of RNA splicing.These results suggest that people lost the ability to maintain normal immune response level and may explain a higher incidence of cancer in the aged population.In terms of the cancer cohort,immune cell abundance,functional exhaustion and inflammatory status in cancer patients,especially young patients showed similar changes to the aging.However,tumors does not accelerate cell senescence,but induce the activation of anti-tumor immune responses and increase the tumor mutation burden than that of healthy people.In short,we characterized the changes of the peripheral immune system during aging and carcinogenesis,and found that age-related immune senescence create conditions for the occurrence and development of cancer.On the other hand,cancer may further accelerates the immune senescence and induce the anti-tumor immune response.