Transcriptome Sequencing Combined With TCGA-BLCA Database To Screen Molecular Markers Related To Bladder Cancer Prognosis

Objective:Molecular markers related to bladder cancer prognosis were screened from transcriptome level by using the second-generation sequencing technology combined with the TCGA-BLCA database,and the possible molecular mechanism regulating bladder cancer progression was discussed.Methods:Collected during June 2018 to December 2018,the second affiliated hospital of kunming medical university urology bladder cancer radical resection patients with carcinoma tissues and adjacent tissues to transcriptome sequencing,the sequencing results joint TCGA-BLCA database,key prognostic screening genes,explore these gene in bladder cancer occurs in the development of molecular mechanisms and clinical significance.Results:1.17 key prognostic genes were identified:ACOX2,ACTA2,ADRA2A,ATP1A2,BUB1B,CCL19,CXCL2,FOXM1,ITGA8,MAD2L1,MAP3K20,MCM4,NPR1,ORC1,PLK4,RASGRP2,TGFB3.2.FOXM1,a key prognostic gene,significantly affects total survival and progression-free survival in bladder cancer patients,with statistically significant differences(P<0.05).3.The clinicopathological characteristics of FOXM1:both linear regression and Logistic regression of clinical variables showed that there was a significant relationship between age and stage and FOXM1(P<0.05),but there was no significant correlation between gender.BMI.smoking history,number of smoking packs per year,number of lymph nodes and FOXM1(P>0.05).FOXMI and clinical variables were significantly associated with total survival and progression-free survival(P<0.05),and high expression of FOXM1 was a risk factor for total survival and progression-free survival.After adjusting for age and stage,FOXMI was not significantly associated with total survival and progression-free survival(P>0.05).The interaction between FOXM1 and age significantly increased the risk of progression-free survival in patients(P<0.05),and the interaction between FOXM]and disease stage significantly increased the risk of total survival and progression-free survival in patients(P<0.05).4.FOXMI transcription regulation:FOXM1 is positively regulated by upstream genes E2F1 and SP1,and leads to high expression of downstream CCNB1,CDC6 and other genes,which are mainly involved in cell cycle,p53 signaling pathway and FoxO signaling pathway,and up-regulation of these pathways may lead to bladder cancer progressionConclusions:1.ACOX2,ACTA2,ADRA2A,ATP1A2,BUB1B,CCL19,CXCL2.ITGA8,MAD2L1,MAP3K20,MCM4,NPR1,ORC1,PLK4,RASGRP2,TGFB3 genes affect only one aspect of total survival or progression-free survival.2.FOXM1 affects both total and progression-free survival and is a molecular marker for bladder cancer prognosis.3.FOXM1 is mainly positively regulated by E2F1 and SP1,and leads to high expression of downstream CCNB1,CDC6 and other genes,which are mainly involved in cell cycle,p53 signaling pathway and FoxO signaling pathway,thus affecting bladder cancer progression.