title: Identifying the role of Wilms tumor 1 associated protein in cancer prediction using integrative genomic analyses.
abstract: The Wilms tumor suppressor, WT1 was first identified due to its essential role in the normal development of the human genitourinary system. Wilms tumor 1 associated protein (WTAP) was subsequently revealed to interact with WT1 using yeast two-hybrid screening. The present study identified 44 complete WTAP genes in the genomes of vertebrates, including fish, amphibians, birds and mammals. The vertebrate WTAP proteins clustered into the primate, rodent and teleost lineages using phylogenetic tree analysis. From 1,347 available SNPs in the human WTAP gene, 19 were identified to cause missense mutations. WTAP was expressed in bladder, blood, brain, breast, colorectal, esophagus, eye, head and neck, lung, ovarian, prostate, skin and soft tissue cancers. A total of 17 out of 328 microarrays demonstrated an association between WTAP gene expression and cancer prognosis. However, the association between WTAP gene expression and prognosis varied in distinct types of cancer, and even in identical types of cancer from separate microarray databases. By searching the Catalogue of Somatic Mutations in Cancer database, 65 somatic mutations were identified in the human WTAP gene from the cancer tissue samples. These results suggest that the function of WTAP in tumor formation may be multidimensional. Furthermore, signal transducer and activator of transcription 1, forkhead box protein O1, interferon regulatory factor 1, glucocorticoid receptor and peroxisome proliferator-activated receptor γ transcription factor binding sites were identified in the upstream (promoter) region of the human WTAP gene, suggesting that these transcription factors may be involved in WTAP functions in tumor formation.
authors.affiliation: Department of General Surgery, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230001, P.R. China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Qian
authors.affiliation: Department of General Surgery, The First Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002, P.R. China.
authors.forename: Minghai
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D023281:Genomics / Q000379:methods; D006801:Humans; D015201:Meta-Analysis as Topic; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011485:Protein Binding; D040901:Proteomics / Q000379:methods; D000072260:RNA Splicing Factors; D014157:Transcription Factors / Q000378:metabolism; D014714:Vertebrates
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D014157:Transcription Factors; C419554:WTAP protein, human