title: Copy number loss of FBXW7 is related to gene expression and poor prognosis             in esophageal squamous cell carcinoma.
abstract: FBXW7 is a tumor suppressor gene that plays a role in cell cycle regulation             via Myc degradation. However, the clinical significance of FBXW7 in esophageal             squamous cell carcinoma (ESCC) has not been evaluated. The purpose of this study             was to assess the clinical significance of FBXW7 for prognosis in human ESCC.             Real-time RT-PCR was used to examine the expression of FBXW7 to determine its             clinicopathological significance in 75 cases of ESCC. Overall survival rate was             calculated using the Kaplan-Meier method, while multivariate survival was analyzed             with the Cox hazard model. FBXW7 suppression analysis was performed to examine             proliferation potency and Myc expression in the FBXW7 siRNA groups. The relationship             between FBXW7 expression and the copy number loss of FBXW7 was examined in clinical             samples of ESCC. Finally, FBXW7 copy number loss was linked to prognosis in 42             ESCC patients. FBXW7 expression in cancer was lower compared to non-cancer tissues             (P=0.003) and is an independent prognostic factor. The proliferation rates and             Myc protein expression were significantly enhanced in FBXW7 siRNA cells compared             to the controls. Cases with a loss of FBXW7 copy number had low FBXW7 expression             and a poorer prognosis than cases with no loss of copy number. Genetic alterations             in esophageal cancer lead to the loss of FBXW7 expression and increased cell proliferation.             These genetic alterations of FBXW7 status may provide a prognostic factor for             ESCC patients.
authors.affiliation: Department of Surgery, Medical Institute of Bioregulation, Kyushu                     University, 4546 Tsurumihara, Beppu 874-0838, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokobori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Toh
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwaya
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Onoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Keiichi I
authors.initials: KI
authors.lastname: Nakayama
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D044767:Ubiquitin-Protein Ligases