Abstract
BackgroundKiSS-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.MethodsWe 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.ResultsStrong 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.ConclusionStrong 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.
Highlights
KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells
The KiSS-1 gene product was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor known as GPR54[9], AXOR12[10], or hOT7T175[11]
We investigated immunohistochemical expression of the KiSS-1 gene product and that of GPR54 in pancreatic cancer tissues obtained by surgical resection
Summary
KiSS-1 was identified as a metastasis-suppressing gene in melanoma cells. The KiSS1 gene product (metastin) was isolated from human placenta as the ligand of GPR54, a G-proteincoupled receptor. Most patients with pancreatic cancer have locally advanced tumors, metastases, or both at the time of diagnosis. To improve the survival of patients with pancreatic cancer, we need a new strategy for the treatment of advanced disease that is unsuitable for surgical resection. In 1996, KiSS-1 was identified as a human metastasis-suppressing gene in melanoma cells[7] and breast cancer cells[8]. The KiSS-1 gene product was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor known as GPR54[9], AXOR12[10], or hOT7T175[11]. KiSS-1 encodes a 145amino acid peptide which is further processed to a C-terminally amidated peptide with 54 amino acids called metastin[11] or kisspeptin-54, as well as to peptides with 14 amino acids (kisspeptin-14) and 13 amino acids (kisspeptin-13)[9]
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