title: Transcriptome profiling of a multiple recurrent muscle-invasive urothelial carcinoma of the bladder by deep sequencing.
abstract: Urothelial carcinoma of the bladder (UCB) is one of the commonly diagnosed cancers in the world. The UCB has the highest rate of recurrence of any malignancy. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of UCB recurrence and is a key step to discovering biomarkers for diagnosis and therapeutic targets. Compared with microarray technology, which is commonly used to identify expression level changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing. In this study, we performed high-throughput transcriptome sequencing at ∼50× coverage on a recurrent muscle-invasive cisplatin-resistance UCB tissue and the adjacent non-tumor tissue. The results revealed cancer-specific differentially expressed genes between the tumor and non-tumor tissue enriched in the cell adhesion molecules, focal adhesion and ECM-receptor interaction pathway. Five dysregulated genes, including CDH1, VEGFA, PTPRF, CLDN7, and MMP2 were confirmed by Real time qPCR in the sequencing samples and the additional eleven samples. Our data revealed that more than three hundred genes showed differential splicing patterns between tumor tissue and non-tumor tissue. Among these genes, we filtered 24 cancer-associated alternative splicing genes with differential exon usage. The findings from RNA-Seq were validated by Real time qPCR for CD44, PDGFA, NUMB, and LPHN2. This study provides a comprehensive survey of the UCB transcriptome, which provides better insight into the complexity of regulatory changes during recurrence and metastasis.
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Genetic Disease, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
authors.forename: Yanxuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Shanghai Claison Bio-Technology, Shanghai, China.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Shunlan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Ying'ai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Sifang
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Jindong
authors.initials: J
authors.lastname: Li
authors.affiliation: Affiliated Haikou Hospital, Xiangya School of Medicine Central South University, Haikou Municipal People's Hospital, Haikou, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Bai
mesh_terms: D000368:Aged; D017398:Alternative Splicing; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D019295:Computational Biology; D019008:Drug Resistance, Neoplasm; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D063990:Gene Ontology; D052138:Genes, Neoplasm / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D009132:Muscles / Q000473:pathology*; D009361:Neoplasm Invasiveness; D012008:Recurrence; D017423:Sequence Analysis, RNA; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology*
chemical_list: D002945:Cisplatin