MP54-09 TM4SF1 IS A NOVEL BIOMARKER FOR HUMAN MUSCLE INVASIVE BLADDER CANCER (MIBC)

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2018MP54-09 TM4SF1 IS A NOVEL BIOMARKER FOR HUMAN MUSCLE INVASIVE BLADDER CANCER (MIBC) Rui Cao, Gang Wang, Kaiyu Qian, Liang Chen, Yu Xiao, and Xinghuan Wang Rui CaoRui Cao More articles by this author , Gang WangGang Wang More articles by this author , Kaiyu QianKaiyu Qian More articles by this author , Liang ChenLiang Chen More articles by this author , Yu XiaoYu Xiao More articles by this author , and Xinghuan WangXinghuan Wang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1700AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES BCa is a heterogeneous disease: non-muscle-invasive bladder cancer (NMIBC) that usually recur but rarely process, and muscle-invasive bladder cancer (MIBC) that progress quickly. Recent studies identify numerous clinical variables and molecular biomarkers, such as chromosomal markers, genetic variations or epigenetic alterations for prediction of its occurrence and recurrence. However, effective biomarkers to distinguish MIBC from NMIBC are urgently needed. Transmembrane-4-L-Six-Family-1 (TM4SF1) is a member of L6 family, which functions as signal transducer to regulate cell development, growth and motility. The aim of the study is to investigate the TM4SF1 as the specific biomarker of MIBC via bioinformatics analysis. METHODS Through mining the big data from GEO and TCGA, a specific MIBC differentially expressed gene (DEG) called TM4SF1 was screened by R and validated by oncomine database, etc. Then qRT-PCR, immunofluorescence and immunohistochemistry analysis were used to detect the transcription and translation level of TM4SF1 in bladder tissues. Clinical correlation was measured by connecting the expression of TM4SF1 with patients′ information. Moreover, TM4SF1 knockdown and overexpression BCa cell model was established by gene regulation. Then flow cytometry, CCK-8 assay, western blot, etc. were used to detect cell cycle distribution, cell growth and related protein expression in vitro. Furthermore, the xenograft model was used to measure the tumor growth of BCa cells transplantation in vivo. RESULTS Our results suggested that TM4SF1 was strongly upregulated in MIBC tissues, corroborated with transcriptome analysis. Moreover, tissue microarray (TMA) showed significant correlations between TM4SF1 with T stage, TNM stage, lymph node metastasis status and survival rate of MIBC patient. Furthermore, in vitro and in vivo studies suggested that proliferation of human bladder cancer (BCa) cells was significantly suppressed by downregulated TM4SF1. Functionally, reduction of TM4SF1 could induce cell cycle arrest and apoptosis possibly via upregulation of reactive oxygen species (ROS) in the BCa cells. Interestingly, these observations were scavenged by treatment of GW9662 (antagonist of PPARγ) and resveratrol (activator of SIRT1), respectively. CONCLUSIONS We have first shown tumor promoting effect of TM4SF1 on MIBC. TM4SF1 could be a biomarker to predict the survival rate of MIBC patients and malignancy of the tumor. And our study suggest that the regulation of ROS metabolism and cell cycle for TM4SF1 in BCa cells was mediated by PPARγ-SIRT1 feedback loop. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e715 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Rui Cao More articles by this author Gang Wang More articles by this author Kaiyu Qian More articles by this author Liang Chen More articles by this author Yu Xiao More articles by this author Xinghuan Wang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...