title: Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender.
abstract: BACKGROUND
  We have previously reported that colonic pericryptal microvascular blood flow is augmented in the premalignant colonic epithelium, highlighting the increased metabolic demand of the proliferative epithelium as a marker of field carcinogenesis. However, its molecular basis is unexplored. In this study, we assessed the expression of a regulator of the "lipogenic switch," fatty acid synthase (FASN), in early colon carcinogenesis for its potential biomarker utility for concurrent neoplasia.
  
  
  METHODS
  FASN expression (IHC) in the colonic epithelium from azoxymethane and polyposis in rat colon (Pirc) models of colorectal cancer was studied. FASN mRNA expression from endoscopically normal rectal mucosa was evaluated and correlated with colonoscopic findings (pathologic confirmation of neoplasia).
  
  
  RESULTS
  FASN expression progressively increased from premalignant to malignant stage in the azoxymethane model (1.9- to 2.5-fold; P < 0.0001) and was also higher in the adenomas compared with adjacent uninvolved mucosa (1.8- to 3.4-fold; P < 0.001) in the Pirc model. Furthermore, FASN was significantly overexpressed in rectal biopsies from patients harboring adenomas compared with those with no adenomas. These effects were accentuated in male (∼2-fold) and obese patients (1.4-fold compared with those with body mass index < 30). Overall, the performance of rectal FASN was excellent (AUROC of 0.81).
  
  
  CONCLUSIONS
  FASN is altered in the premalignant colonic mucosa and may serve as a marker for colonic neoplasia present elsewhere. The enhanced effects in men and obesity may have implications for identifying patient subgroups at risk for early-onset neoplasia.
  
  
  CONCLUSIONS
  These findings support the role of rectal FASN expression as a reliable biomarker of colonic neoplasia.
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Mart Dela
authors.initials: MD
authors.lastname: Cruz
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts. rwali@bu.edu.
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Wali
authors.affiliation: Department of Medicine, NorthShore University HealthSystem, Evanston, Illinois.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Bianchi
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Radosevich
authors.affiliation: Department of Pathology, St. Louis University, St. Louis, Missouri.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Crawford
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Lisa
authors.initials: L
authors.lastname: Jepeal
authors.affiliation: Department of Medicine, NorthShore University HealthSystem, Evanston, Illinois.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goldberg
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Weinstein
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Navneet
authors.initials: N
authors.lastname: Momi
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Priya
authors.initials: P
authors.lastname: Roy
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Audrey H
authors.initials: AH
authors.lastname: Calderwood
authors.affiliation: Biomedical Engineering Department, Northwestern University, Evanston, Illinois.
authors.forename: Vadim
authors.initials: V
authors.lastname: Backman
authors.affiliation: Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts.
authors.forename: Hemant K
authors.initials: HK
authors.lastname: Roy
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D064429:Fatty Acid Synthases / Q000378:metabolism*; D006801:Humans; D008297:Male; D009765:Obesity / Q000150:complications* / Q000473:pathology; D051381:Rats
chemical_list: D014408:Biomarkers, Tumor; D064429:Fatty Acid Synthases