Construction Of Immune Subtype By Combing Molecular Subtype And Immune Classification In Muscle-invasive Bladder Cancer

BackgroundThe discovery and development of tumor subtypes is an important part of the current personalized treatment of cancer.Accurate classification of patients with invasive bladder cancer into different tumor subtypes can provide reference value for clinical decision.With the rapid development of gene sequencing technology,researchers have more access to get and analysis high-throughput sequencing data of cancer patients,which creating opportunities to discover individual differences in gene expression and tumorigenesis,development and metastasis mechanisms at the genetic level.At present,immunotherapy based on immunological checkpoint inhibitors has received increasing attention in the treatment of bladder cancer,but immunotherapy has a lower response rate to overall bladder cancer patients.Therefore,establishing the immune subtype that can predict the benefit of patients under immunotherapy is urgently needed for patients and doctors.MethodThe sequencing data of 403 tumor tissues derived from the TCGA database were download and used as the training set,the tumor molecular subtypes were obtained by cluster analysis;the immune classification was constructed by using CD8+ T cell and TMB(tumor mutation burden)value;Tumor molecular subtypes and immune classification were combined to construct immune subtype of muscle invasive bladder cancer.The immune subtypes provided in the study were assessed by survival analysis,clinical response records,immune checkpoint genes expression,and immune-related indicators values.The clinical trial data of 234 metastatic bladder cancer patients treatedwith PD-1 were downloaded and taken as a validation set.The immune subtype constructed by training dataset was further validated by clinical benefit in the validation dataset.ResultsIn the TCGA dataset,48%(193/403)ofthe MIBC(muscle invasive bladder cancer)patients were clustered as Basal(basal)subtypes,while 52%(210/403)patients were Luminal(luminal)subtypes.Basal subtype related genes are mainly enriched in related physiological processes such as tumor invasion,metastasis and immunity.Higher CD8+ T cell and higher TMB values were positively associated with benign outcomes in bladder cancer patients.Immune classification was obtained by median value of immune features:Type ?(CD8+Thigh/TMBhigh),Type ?(CD8+Thigh/TMBlow;CD8+Tlow/TMBhigh),Type ?(CD8+Tlow/TMBlow).The overall survival of Type ?patients was significantly better than Type ? and Type ? patients.The immune subtype was constructed based on the molecular subtypes and the immune classification.The Basal? subtype patients have the highest objective response rate and better prognosis when compared with other immune subtypes.Besides,its objective response rate is superior to the immunological typing Type ?.Conclusion1.There are two molecular subtypes with distinct characteristics in invasive bladder cancer.The Basal subtype has a higher pathological grade than the Luminal subtype,with a higher degree of malignancy and a worse prognosis.2.In bladder cancer tissues,CD8+ T cell fraction and TMB value are independent prognostic factors.3.Among the immune classfications,Type ? has significantly better objective response rate and prognosis for immunotherapy than Type ? and Type ?.4.The objective response rate and prognosis of Basal? subtype is significantly better than other subtypes,and the objective response rate is 67%.Therefore,the immune subtypes can be used as a pre-treatment evaluation for immune checkpoint inhibitors uterlization.