title: Prognostic value of metastin expression in human pancreatic cancer.
abstract: BACKGROUND
  KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS-1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-protein-coupled receptor. The role of metastin and GPR54 in tumor progression is not fully understood.
  
  
  METHODS
  We investigated the clinical significance of metastin and GPR54 expression in pancreatic cancer. We evaluated immunohistochemical expression of metastin and GPR54 in pancreatic ductal adenocarcinoma tissues obtained from 53 consecutive patients who underwent resection between July 2003 and May 2007 at Kyoto University Hospital. In 23 consecutive patients, the plasma metastin level was measured before surgery by enzyme immunoassay.
  
  
  RESULTS
  Strong immunohistochemical expression of metastin was detected in 13 tumors (24.5%), while strong expression of GPR54 was detected in 30 tumors (56.6%). Tumors that were negative for both metastin and GPR54 expression were significantly larger than tumors that were positive for either metastin or GPR54 (p = 0.047). Recurrence was less frequent in patients who had metastin-positive tumors compared with those who had metastin-negative tumors (38.5% versus 70.0%, p = 0.04). Strong expression of metastin and GPR54 was significantly correlated with longer survival (p = 0.02). Metastin expression by pancreatic cancer was an independent prognostic factor for longer survival (hazard ratio, 2.1; 95% confidence interval, 1.1-4.7; p = 0.03), and the patients with a high plasma metastin level (n = 6) did not die after surgical resection.
  
  
  CONCLUSIONS
  Strong expression of metastin and GPR54 by pancreatic cancer is associated with longer survival. Metastin expression is an independent prognostic factor for the survival of pancreatic cancer patients. The plasma metastin level could become a noninvasive prognostic factor for the assessment of pancreatic cancer.
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan. kaznagai@kuhp.kyoto-u.ac.jp
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nagai
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Doi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Koizumi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Masui
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tomita
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006262:Health; D006801:Humans; D007150:Immunohistochemistry; D059648:Kisspeptins; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D012008:Recurrence; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins