AUTHOR=Chen Kang , Xing Ji , Yu Weimin , Xia Yuqi , Zhang Yunlong , Cheng Fan , Rao Ting 

TITLE=Identification and Validation of Hub Genes Associated with Bladder Cancer by Integrated Bioinformatics and Experimental Assays

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.782981

DOI=10.3389/fonc.2021.782981

ISSN=2234-943X

ABSTRACT=<p>Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein–protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, <italic>TROAP</italic>, <italic>CENPF</italic>, <italic>PRC1</italic>, <italic>AURKB</italic>, <italic>CCNB2</italic>, <italic>CDC20</italic>, <italic>TTK</italic>, <italic>CEP55</italic>, <italic>ASPM</italic>, and <italic>CDCA8</italic> were identified as candidate central genes. According to the survival analysis, the high expression of <italic>TTK</italic> was related to the poor overall survival (OS) of patients with BC. <italic>TTK</italic> may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of <italic>TTK</italic> was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of <italic>TTK</italic> in BC cells was confirmed <italic>in vitro</italic>. Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC</p>