Overexpression of lysine specific demethylase 1 predicts worse prognosis in primary hepatocellular carcinoma patients

World J Gastroenterol. 2012 Dec 7;18(45):6651-6. doi: 10.3748/wjg.v18.i45.6651.

Abstract

Aim: To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1 (LSD1) in hepatocellular carcinoma (HCC).

Methods: We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. In addition, we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry. The relationship between LSD1 expression, clinicopathological features and patient survival was investigated.

Results: Immunohistochemistry, Western blotting, and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues (P < 0.01). Additionally, immunostaining showed more LSD1-positive cells in the higher tumor stage (T3-4) and tumor grade (G3) than in the lower tumor stage (T1-2, P < 0.001) and tumor grade (G1-2, P < 0.001), respectively. Moreover, HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates (P < 0.001) and lower 5-year disease-free survival rates (P < 0.001), respectively. A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio (HR) = 1.426, 95%CI: 0.672-2.146, P < 0.001] and 5-year overall survival (HR = 2.456, 95%CI: 1.234-3.932, P < 0.001) in HCC.

Conclusion: Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.

Keywords: Hepatocellular carcinoma; Lysine specific demethylase 1; Prognosis; Tumor progression.

MeSH terms

  • Adult
  • Aged
  • Blotting, Western
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Disease-Free Survival
  • Female
  • Histone Demethylases / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction

Substances

  • Histone Demethylases
  • KDM1A protein, human