Prognostic value of metastin expression in human pancreatic cancer.
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.
Nagai
Kazuyuki
K
Department of Hepato-Biliary-Pancreatic Surgery and Transplantation, Kyoto University, Kyoto, Japan. kaznagai@kuhp.kyoto-u.ac.jp
Doi
Ryuichiro
R
Katagiri
Fumihiko
F
Ito
Tatsuo
T
Kida
Atsushi
A
Koizumi
Masayuki
M
Masui
Toshihiko
T
Kawaguchi
Yoshiya
Y
Tomita
Kenji
K
Oishi
Shinya
S
Fujii
Nobutaka
N
Uemoto
Shinji
S
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*
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