title: Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma.
abstract: BACKGROUND
  Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in OSCC.
  
  
  METHODS
  We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery.
  
  
  RESULTS
  The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P=0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic factors for OSCC patients.
  
  
  CONCLUSIONS
  These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: D
authors.initials: D
authors.lastname: Fukuma
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: K
authors.initials: K
authors.lastname: Ota
authors.forename: A
authors.initials: A
authors.lastname: Hiraki
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
mesh_terms: D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D009062:Mouth Neoplasms / Q000378:metabolism*; D011379:Prognosis; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation
chemical_list: D051034:Inhibitor of Apoptosis Proteins; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D005472:Fluorouracil