Down-regulation of EGFL8: a novel prognostic biomarker for patients with colorectal cancer

Anticancer Res. 2011 Jun;31(6):2249-54.

Abstract

Background: In a previous study, we reported a critical role of epidermal growth factor-like domain 7 (EGFL7) in the metastasis of hepatocellular carcinoma (HCC) and documented it to be a prognostic biomarker as well as a potential therapeutic target for HCC. However, the role of EGFL8, the only known paralog of EGFL7, in human malignancies is currently unclear.

Patients and methods: EGFL8 expression in 101 cases of colorectal cancer (CRC) patients was determined by quantitative reverse transcription-polymerase chain reaction and the clinicopathological features of the CRC patients were correlated with the EGFL8 down-regulation scores. In addition, the survival curve and Cox regression model were also employed to assess the prognostic value of EGFL8 down-regulation.

Results: EGFL8 was significantly decreased in CRC tissues (p<0.0001) and the down-regulation of EGFL8 was evidenced in 74.3% (75/101) of the CRC patients. EGFL8 down-regulation correlated significantly to distant metastasis (p=0.038) and high TNM stage (p=0.012) of CRC. The CRC patients with high EGFL8 down-regulation showed either poorer disease-free survival (p=0.0167) or poorer overall survival (p=0.0310) than those with low EGFL8 down-regulation. Multivariable analysis identified EGFL8 down-regulation as an independent prognostic factor for CRC patients (hazard ratio, 12.974; p=0.037).

Conclusion: The reduced expression of EGFL8 is closely related to metastastic potential and poor prognosis of CRC, suggesting the down-regulation of EGFL8 as a novel prognostic biomarker for CRC patients.

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Calcium-Binding Proteins
  • Case-Control Studies
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • EGF Family of Proteins
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • EGF Family of Proteins
  • EGFL8 protein, human
  • Endothelial Growth Factors