title: Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer.
abstract: OBJECTIVE
  To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer.
  
  
  METHODS
  One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ² test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer.
  
  
  RESULTS
  Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively).
  
  
  CONCLUSIONS
  KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.
authors.affiliation: School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leics LE12 5RD, United Kingdom.
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Lu-Tao
authors.initials: LT
authors.lastname: Du
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wang
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Yang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhao-Gang
authors.initials: ZG
authors.lastname: Dong
authors.forename: Gui-Xi
authors.initials: GX
authors.lastname: Zheng
authors.forename: Chuan-Xin
authors.initials: CX
authors.lastname: Wang
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051741:Kruppel-Like Transcription Factors; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C507402:KLF8 protein, human; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins
keywords: Angiogenesis; Gastric cancer; Krüppel-like factor 8; Prognosis