title: Homeobox-Only Protein Expression Is a Critical Prognostic Indicator of Pancreatic Neuroendocrine Tumor and Is Regulated by Promoter DNA Hypermethylation.
abstract: We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET).
  
  
  
  We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance.
  
  
  
  (1) Homeobox-only protein is strongly expressed on pancreatic islet cells by immunohistochemistry (IHC). Homeobox-only protein expression was recognized on pNET tumor cells for 1+ in 15, for 2+ in 16, and for 3+ in 5. (2) Homeobox-only protein IHC expression was significantly associated with prognosis (P = 0.03), and survival rate was 37.5%, 70.3%, and 100% in HOPX 1+, 2+, and 3+, respectively. (3) Promoter DNA methylation was quantitatively assessed, and HOPX hypermethylation is found in 6.3%, 11.8%, and 66.7% of G1/G2/G3 pNET, respectively (P = 0.02). (4) Multivariate Cox proportional hazards model identified HOPX IHC expression and HOPX promoter DNA hypermethylation as independent prognostic factors in pNET.
  
  
  
  Homeobox-only protein expression is a critical prognostic indicator of pNET, and its regulation may be made through promoter DNA methylation.
authors: From the Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors: Hideki
authors: H
authors: Ushiku
authors: Keishi
authors: K
authors: Yamashita
authors: Hiroshi
authors: H
authors: Kawamata
authors: Mina
authors: M
authors: Waraya
authors: Hiroshi
authors: H
authors: Katoh
authors: Keigo
authors: K
authors: Yokoi
authors: Toshimichi
authors: T
authors: Tanaka
authors: Satoru
authors: S
authors: Ishii
authors: Nobuyuki
authors: N
authors: Nishizawa
authors: Mariko
authors: M
authors: Kikuchi
authors: Naoko
authors: N
authors: Minatani
authors: Ken
authors: K
authors: Kojo
authors: Hiroshi
authors: H
authors: Tajima
authors: Ryo
authors: R
authors: Nishiyama
authors: Takashi
authors: T
authors: Kaizu
authors: Yusuke
authors: Y
authors: Kumamoto
authors: Masahiko
authors: M
authors: Watanabe
mesh_terms: D004247:DNA; D019175:DNA Methylation; D005801:Genes, Homeobox; D006801:Humans; D010190:Pancreatic Neoplasms; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D004247:DNA