Comprehensive Genetic Analysis Of Difference In Efficacy Of Gemcitabine In Invasive Bladder Cancer

ObjectiveBladder cancer is a common malignant tumor of the urinary system.The treatment of patients with invasive bladder cancer mainly included systemic chemotherapy and local perfusion therapy.Gemcitabine is a commonly used chemotherapeutic drug,which plays an important role in the treatment of invasive bladder cancer,but responses of different patients to gemcitabine chemotherapy are different,and the reason is not clear.Based on the clinical problem,this study comprehensively analyzes the genetic factors affecting the difference in the efficacy of gemcitabine in the treatment of invasive bladder cancer at the genome and transcriptome level.MethodsDownload clinical data,genome sequencing data,and RNA expression data of 412 bladder cancer patients from The Cancer Genome Atlas(TCGA)database.Screen patients according to the inclusion and exclusion criteria.Use the genomic data to map the tumor mutation landscape of patients.Grouped by disease-free survival time.The differentially expressed genes that affect the efficacy ware screened out,and the differential genes ware enriched and analyzed.Constructed a weighted gene co-expression network.Analyzed the relationship between gene function modules and survival traits.Screen key genes and pathways that have the greatest effect on the difference in the efficacy of gemcitabine in the treatment of bladder cancer.ResultsGenomic analysis found that patients had different tumor mutation landscapes in different survival groups,and the tumor mutation load was higher in the longer survival group(p=0.01361).Transcriptome analysis further found that the difference in the efficacy of gemcitabine administration has its unique differentially expressed genes.WGCNA identified co-expressing functional modules related to the disease-free survival characteristics of patients.The pathways enriched by these modules are cell cycle regulation(p=9.80E-14),metabolic processes(p=2.58E-7),focal plaques(p=4.33E-8)and tissue migration(p=2.46E-12).Finally,twenty Hub genes PHF19,H2AFV,KHDRBS1,NUSAPI,SMC4,GLTP,EMPI,KRTIO,AQP3,CBRI,OLFML2B,COL5A2,COL3A1,ADAM12,THYl,MYH11,CNN1,ACTG2,MYL9,TNS1 ware screed as predictor of gemcitabine efficacy.ConclusionsBy studying the res,ponsiveness of patients with aggressive bladder cancer,it was found that patients with a higher tumor mutation load had better response to gemcitabine and longer survival.Patients' genetic differences will affect the efficacy of drugs.In this study,the expression of cell cycle regulatory genes,metabolic process regulatory genes,tissue adhesion,invasion,and migration-related genes were related to disease free survival.All of these findings have potential value for treatment options of patients with aggressive bladder cancer.Figure 9 table 8 reference 66...