title: Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer.
abstract: BACKGROUND
  Aldehyde dehydrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections.
  
  
  METHODS
  Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data.
  
  
  RESULTS
  qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival.
  
  
  CONCLUSIONS
  Immunohistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer.
authors.affiliation: Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. christoph.kahlert@med.uni-heidelberg.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Janine
authors.initials: J
authors.lastname: Beck
authors.forename: Thilo
authors.initials: T
authors.lastname: Welsch
authors.forename: Carolin
authors.initials: C
authors.lastname: Mogler
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Shamik
authors.initials: S
authors.lastname: Dutta
authors.forename: Thomas
authors.initials: T
authors.lastname: Niemietz
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002455:Cell Division; D045744:Cell Line, Tumor / Q000201:enzymology; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016016:Proportional Hazards Models; D050697:Retinal Dehydrogenase
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase