title: Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic biomarker in gastrointestinal stromal tumor.
abstract: BACKGROUND
  Prognostic biomarkers are required for risk stratification therapy in the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed to identify prognostic biomarkers in GIST. We assessed the prognostic value of E twenty-six variant 1 (ETV1), a recently identified transcription factor unique to GIST. We also examined the clinical utility and functions of its downstream gene, potassium channel tetramerization domain containing protein 10 (KCTD10).
  
  
  METHODS
  The levels of ETV1 and KCTD10 were evaluated immunohistochemically in 112 patients with GIST treated at two hospitals. The functional properties of KCTD10 were examined by gene silencing assay in cultured GIST cells.
  
  
  RESULTS
  Immunohistochemistry revealed that ETV1 expression in GIST had no prognostic significance. In contrast, the disease-free survival rate was 88.5% in patients with KCTD10-positive tumors and 55.8% in those with KCTD10-negative tumors (p <0.0001). KCTD10 was an independent prognostic factor (p <0.05). In the low-risk classification group, KCTD10 was significantly associated with favorable prognosis (p = 0.0008). Gene silencing of KCTD10 increased cell proliferation and invasion, suggesting that KCTD10 has a tumor-suppressive function.
  
  
  CONCLUSIONS
  The GIST-specific transcription factor ETV1 may have no prognostic potential, whereas its downstream gene KCTD10 is associated with a favorable prognosis. Our study indicated the novel prognostic utility of KCTD10 in GIST, and suggested its tumor-suppressive effects on GIST cells. Further validation studies of KCTD10 for clinical applications, and functional verification of KCTD10 for better understanding of molecular basis of malignant phenotypes are worth challenging in GIST.
authors: Division of Pharmacoproteomics, National Cancer Centre Research Institute, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Kubota
authors: Akihiko
authors: A
authors: Yoshida
authors: Hitoshi
authors: H
authors: Tsuda
authors: Yoshiyuki
authors: Y
authors: Suehara
authors: Taketo
authors: T
authors: Okubo
authors: Tsuyoshi
authors: T
authors: Saito
authors: Hajime
authors: H
authors: Orita
authors: Koichi
authors: K
authors: Sato
authors: Takahiro
authors: T
authors: Taguchi
authors: Takashi
authors: T
authors: Yao
authors: Kazuo
authors: K
authors: Kaneko
authors: Hitoshi
authors: H
authors: Katai
authors: Akira
authors: A
authors: Kawai
authors: Tadashi
authors: T
authors: Kondo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D012307:Risk Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C539187:KCTD10 protein, human; D024642:Potassium Channels, Voltage-Gated; D034741:RNA, Small Interfering; D014157:Transcription Factors
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