| The incidence of bladder cancer is high,and it is easy to relapse and metastasis,which causes physical and mental damage and economic burden to patients.But the current treatment methods,whether chemotherapy,surgical resection,or immunotherapy,are limited in their effect.The effect also varies from person to person.One of the important reasons for this is tumor heterogeneity.Intratumoral heterogeneity is an important mechanism for the survival and evolution of tumor,which has been determined to be related to the survival and prognosis of patients with most types of cancer,including bladder cancer.Therefore,studying the heterogeneity in the progression of bladder cancer and identifying the key molecules and cell subsets that cause the progression of bladder cancer is particularly important for the prognosis and accurate treatment of patients with bladder cancer.The traditional sequencing technology can only focus on the mixed state of a large number of tissue samples,while ignoring the problem that there may be many different cells in the sample.Single-cell transcriptome sequencing,aiming at this bottleneck,can provide information about the state of individual cells in tissues,and is a key technology for exploring intra-tumor heterogeneity.The heterogeneity of bladder cancer cells is a key factor for tumor survival and prognosis,but the number of single-cell studies on bladder cancer is limited and the corresponding clinical prognosis information is lacking.To solve this problem,this study combines single cell analysis with clinical information from a large number of data to explore the genealogical diversity of bladder cancer and its prognostic significance.We sequenced 12,424 normal bladder cells and identified 11 cell types and 5epithelial subsets,including basal cells,intermediate cells,umbrella cells,TNNT1+epithelial cells,and EMT-like cells,and constructed a complete bladder single cell transcriptome map.Deconvolution analysis was then used to estimate the cell types and epithelial lineages in the RNA-seq cohort of bulk transcripts of bladder cancer,and then the composition of the epithelial lineage of bladder cancer in each sample was calculated to explore the cell pedigree status of bladder cancer.Based on the intratumoral heterogeneity of bladder cancer,we integrated the RNA-seq clinical data of tumor lineage and the batch clinical data sets such as TCGA,MSKCC,and GEO databases to study the relationship between tumor cell lineage and the tumorigenesis and patient prognosis,and further determined the cancer subtypes of clinical significance.We found that there were a large number of umbrella cells in patients with bladder cancer in the early stage,while the number of EMT-like cells increased significantly in the late stage.In addition,the proportion of EMT-like subtypes in highgrade tumors was higher than that in low-grade tumors.Similarly,in survival analysis,EMT-like subtypes were associated with poor prognosis,while umbrella cell subtypes were associated with longer survival.EMT-like subtypes were widely enriched in carcinogen-related pathways such as cell migration,TNFA signal transduction,angiogenesis,and hypoxia,while umbrella subtypes were widely rich in immunerelated pathways such as immune effect proof,cytokine response,antigen processing,and presentation,IL2 and STAT5 signal transduction,which were all related to tumor inhibition.These biological processes explained how cancer pedigree guides the internal mechanism of tumor progression and patient prognosis.In conclusion,this study showed the single cell map of the human bladder by sc RNA-seq,and combined with batch transcriptome data,revealed the relationship between cell subtypes and tumor cell lineage.Cancer subtypes with important prognostic significance were identified.Our study provided a new idea for the accurate treatment of bladder cancer. |
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