title: Associations between markers of colorectal cancer stem cells, mutation, microRNA and the clinical features of ulcerative colitis.
abstract: OBJECTIVE
  Several factors have been implicated in the pathogenesis of colorectal cancer (CRC) associated with ulcerative colitis (UC). We investigated markers of cancer cell pluripotency, including CD44 and CD166, microRNA-21 (miR-21) and microRNA-215 (miR-215), and APC, K-ras and DCC mutations in biopsy specimens from patients with UC to evaluate any correlations with clinical risk factors.
  
  
  METHODS
  We observed 18 patients with UC and collected two biopsy specimens from each patient at diagnosis and at a follow-up end-point. We examined the expression of CD44, CD166, miR-21 and miR-215, and APC, K-ras and DCC mutations. We compared these markers at the two time points and assessed their associations with clinical characteristics, including the duration of colitis, histological alterations and the age of the patient at the onset of UC.
  
  
  RESULTS
  Most (16/18) patients had alleviation of mucosal inflammation or remained stable during follow-up; one patient developed dysplasia and one had severe aggravation of the lesion during follow-up. Enhanced expression of CD44, CD166 and miR-21 with miR-215 was found in the specimens obtained at follow-up, despite alleviation of mucosal lesions. Coherence of cancer stem cell markers and miRNAs was seen in patients who had significant worsening of inflammation, dysplasia and a long duration of colitis. APC mutation occurred in only one patient; this patient had the longest duration of UC (23 years).
  
  
  CONCLUSIONS
  Enhanced markers of CRC in follow-up colonic mucosal samples support the conclusion that the duration of UC plays the most important role in UC-related carcinogenesis.
authors.affiliation: Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology and Department of Internal Medicine, Veterans Administration Medical Center, Detroit, Michigan, USA.
authors.forename: E
authors.initials: E
authors.lastname: Levi
authors.affiliation: Division of Gastroenterology and Department of Internal Medicine, Veterans Administration Medical Center, Detroit, Michigan, USA.|Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Du
authors.affiliation: Department of Pathology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: H H
authors.initials: HH
authors.lastname: Zhou
authors.affiliation: Division of Gastroenterology and Department of Internal Medicine, Veterans Administration Medical Center, Detroit, Michigan, USA.|Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: R
authors.initials: R
authors.lastname: Miller
authors.affiliation: Division of Gastroenterology and Department of Internal Medicine, Veterans Administration Medical Center, Detroit, Michigan, USA.|Wayne State University School of Medicine, Detroit, Michigan, USA.|Karmanos Cancer Institute, Detroit, Michigan, USA.
authors.forename: A P N
authors.initials: AP
authors.lastname: Majumdar
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000502:physiology; D011230:Precancerous Conditions / Q000235:genetics*; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: APC mutation; Ulcerative colitis; cancer stem cells; carcinogenesis; colorectal cancer; miR-21