title: Aldehyde dehydrogenase 1 is associated with recurrence-free survival but not stem cell-like properties in hepatocellular carcinoma.
abstract: OBJECTIVE
  It has been reported that aldehyde dehydrogenase 1 A1 (ALDH1) could be not only a normal stem cell marker but also a cancer stem cell marker. ALDH1 expression could be a predictor of poor prognosis in a wide range of cancers. However, the role of ALDH1 in hepatocellular carcinoma (HCC) remains unclear.
  
  
  METHODS
  We conducted loss-of-function assays for ALDH1 by using short-hairpin RNA in HCC cells and evaluated the correlation between ALDH1 expression and clinicopathological features based on immunohistochemical assessment of 49 primary HCC tissues.
  
  
  RESULTS
  Neither cell proliferation nor the anchorage-independent sphere formation ability of HCC cells were altered after ALDH1 knockdown. Flow cytometric analyses revealed that ALDH1 knockdown showed no remarkable change in the proportion of epithelial cell adhesion molecule (EpCAM)(+)  tumor-initiating cells. Although non-tumor tissues in primary HCC samples diffusely and homogenously expressed ALDH1 at low levels, tumor tissues contained cells with high levels of ALDH1 expression at varying frequencies. Primary HCC samples were categorized as ALDH1-high or ALDH1-low based on the percentage of ALDH1-overexpressing cells. ALDH1-high HCC was characterized by low serum levels of α-fetoprotein (P < 0.01) and well-differentiated pathology (P = 0.03). Multivariate analysis showed that high ALDH1 expression was a favorable prognostic factor in recurrence-free survival of HCC (P = 0.02).
  
  
  CONCLUSIONS
  Our findings show that ALDH1 expression has little association with stem cell-like features in HCC cells. ALDH1 might function as a differentiation marker rather than a stem cell marker in HCC.
authors.affiliation: Departments of Medicine and Clinical Oncology             Cellular and Molecular Medicine             General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan             King's College Hospital, Institute of Liver Studies, Denmark Hill, London, UK.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Suzuki
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyagi
authors.forename: Motohisa
authors.initials: M
authors.lastname: Tada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kanai
authors.forename: Fumio
authors.initials: F
authors.lastname: Imazeki
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka