title: Analyzing the gene expression profile of anaplastic histology Wilms' tumor with real-time polymerase chain reaction arrays.
abstract: BACKGROUND
  Wilms' tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly.
  
  
  METHODS
  A real-time polymerase chain reaction (PCR) array was designed and tested. Next, the gene expression profile of pediatric anaplastic histology WT and normal adjacent tissues were analyzed. These expression data were anlyzed with Multi Experiment View (MEV) cluster software further. Datasets representing genes with altered expression profiles derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool (IPA).
  
  
  RESULTS
  88 real-time PCR primer pairs for quantitative gene expression analysis of key genes involved in pediatric anaplastic histology WT were designed and tested. The gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal controls; we identified 15 genes that are up-regulated and 16 genes that are down-regulated in the former. To investigate biological interactions of these differently regulated genes, datasets representing genes with altered expression profiles were imported into the IPA for further analysis, which revealed three significant networks: Cancer, Hematological Disease, and Gene Expression, which included 27 focus molecules and a significance score of 43. The IPA analysis also grouped the differentially expressed genes into biological mechanisms related to Cell Death and Survival 1.15E(-12), Cellular Development 2.84E(-11), Cellular Growth and Proliferation 2.84E(-11), Gene Expression 4.43E(-10), and DNA Replication, Recombination, and Repair 1.39E(-07). The important upstream regulators of pediatric anaplastic histology WT were TP53 and TGFβ1 signaling (P = 1.15E(-14) and 3.79E(-13), respectively).
  
  
  CONCLUSIONS
  Our study demonstrates that the gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal tissues with real-time PCR array. We identified some genes that are dysregulated in pediatric anaplastic histology WT for the first time, such as HDAC7, and IPA analysis showed the most important pathways for pediatric anaplastic histology WT are TP53 and TGFβ1 signaling. This work may provide new clues into the molecular mechanisms behind pediatric anaplastic histology WT.
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Tao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Shao-Yan
authors.initials: SY
authors.lastname: Hu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, the 5th Hospital of Chinese PLA, Yin chuan, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Du
authors.affiliation: Department of Cell and Molecular Biology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Sun
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Zhao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Xiao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Li-Xiao
authors.initials: LX
authors.lastname: Xu
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Translational Research Center, Second Hospital, The Second Clinical School, Nanjing Medical University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
keywords: HDAC7; Ingenuity pathway analysis; Pediatric anaplastic histology Wilms’ tumor; Real-time PCR array; TGFβ1; TP53