Received: 21 November 2018 Revised: 27 February 2019 Accepted: 6 March 2019 DOE: 10.1002p28546 ORIGINAL RESEARCnes-highdearee of intra modole connecHvity WILEYa Phypliology ARTICLE Four novel biomarkers for bladder cancer identified by weighted gene coexpression network analysis Zi-Xin Guo | Xiao-Ping Liu Sheng Li124 | Yu-Jia Feng | Ying-Jie Zhao3 Xin Yan120 Tong-Zu Liu a cadtin /dsase can be ideiel anatrdy ocurring gere in uohich Department of Urology, Zhongnan Hospital Abstract Bladder cancer (BC) is one of the most malignancies in terms of incidenceCo e recurrence worldwide. The aim of this study is to find out novel and proplostic dvdarn of Wuhan University, Wuhan, China Department of Biological Repositories Zhongnan Hospital of Wuhan University Wuhan, China rst. we identified 258 differentialy expressed biomarkers for patients with BC. genes by using GSE1991 from Gene Expression Omnibus database. pecond, a total of 33 modules were identified by constructing a coexpression network by using weighted gene coexpression network analysisandyellow module was regarded as the Department of Urology, Zunyi Medical University, Zunyl China Human Genetics Resource Preservation Center of Hubei Province, Wuhan, China wnere Corespondence Sheng Li Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 169 Donghu Road 430071 key module. Furthermore, by constructing protein-protein interaction networks, we preliminarily picked out 13 genes. Among them four hub genes (CCNB1, KIF4A TPX2 and TRIP13) were eventually identified by using five different methods (survival analysis, one-way analysis of variance, the Spearman correlation analysis receiver operating characteristic curve, and expression value comparison), which Wuhan, China Email:
[email protected] Funding information were significantly correlated with the prognosis of BCc. The validation of transcrip- National Natural Science Foundation of China Grant/Award Number: 81802541: Zhongnan Hospital of Wuhan University Science Technology and Ienovation Seed Fund, Grant Award Number: ampy2017050: 351 Talent tional and translational levels made sense (based on Oncomine and The Human Protein Atlas database). Moreover,functional enrichment analysis suggested that all- the hub genes played crucial roles in chromosome segregation, sister chromatid segregation, nuclear chromosome segregation mitotic nuclear division nuclear division, and organelle fission during cell mitosis. In addition, three of the hub genes Project of Wuhan University (Luojia Young Scholars: S (KIF4A, TPX2, and TRIP13) might be potential targets of cancer drugs according to the results of the genetical alteration. In conclusion, this study indicates that four hub genes have great predictive value fon the prognosis of BC, and may contribute to the exploration of the further and more in-depth research of BC KEYWORDS bladder cancer, coexpression, histologic grade, hug genes, WGCNA 1 INTRODUCTION cancers (Siegel et al. 2018). For diagnosis, cystoscopy and biopsy are still the gold standard (Emerson & Cheng, 2005). Unfortunately, the Bladder cancer (BC) is the most common malignancy oft the urinary average age for BC at diagnosis is 65 years, which means that most system (Ebrahimi et al, 2019). There are 437,422 new cases annually BCs are diagnosed at an advanced stage (Shadpour, Emami & in the world according to a recent research (Ebrahimi et al, 2019 Haghdani, 2016. Many patients often lost the optimal chance for Although in the country with health facilities well developed, BC most effective treatment. As for the prognosis of BC. the situation was not optimistic. Five-year survivai rate for BC patients was reported as low as 50-70% (Hussein et al, 2016) Moreover, it has causes a lot of troubles (Siegel, Miller, & Jemal, 2018). For example, in the USA, BC is the 13th most common cause of deaths among all 0 2019 Wley Periodicals, Inc. 90738C J Cell Physiol 2019234 19073-19087 wileyonlinelibrary.com/journal/jcp Thee is a So-70% chace that Pe boto Patients suruiue only up to Syrs