title: KISS1 Associates with Better Outcome via Inhibiting Matrix Metalloproteinase-9 in Colorectal Liver Metastasis.
abstract: BACKGROUND
  Cancer metastasis is a major contributor to patient death because of its systemic nature and resistance to therapeutic agents. KISS1, originally identified to be a metastasis suppressor, couples to its receptor KISS1R and plays a pivotal role in suppressing cancer metastasis. In this study, we investigated KISS1 and KISS1R expression in colorectal liver metastasis (CRLM), and analyzed their correlation with patients' clinicopathological variables, including prognosis.
  
  
  METHODS
  Overall, 55 patients with CRLM who underwent hepatectomy between 2003 and 2013 were enrolled in this study. Immunohistochemistry was performed to evaluate the protein expression of KISS1, KISS1R, and matrix metalloproteinase-9 (MMP-9). Clinicopathological variables, including prognosis, were compared between low- and high-expressing groups of KISS1 or KISS1R. We analyzed the correlation of KISS1 or KISS1R protein expression with MMP-9.
  
  
  RESULTS
  Expression of both KISS1 and KISS1R was significantly correlated with overall survival (p = 0.0283 and p = 0.0275, respectively). The 5-year overall survival rate of the KISS1 and KISS1R low groups was 44.3 and 39.3 %, and 73.7 and 67.9 % in the high groups, respectively. Multivariate analysis revealed that KISS1 low expression was an independent prognostic factor (p = 0.037, hazard ratio 0.20). Moreover, KISS1 low-expression patients had more frequent distant metastasis (p < 0.05). Furthermore, KISS1 low-expressing tumor tissues expressed more MMP-9 protein (p = 0.034), which was mainly expressed in neutrophils at the metastatic tumor edge.
  
  
  CONCLUSIONS
  KISS1 could be a promising prognostic and therapeutic marker in CRLM. KISS1 low expression may induce high MMP-9 expression in neutrophils.
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.|Fujii Memorial Institute of Medical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Chengzhan
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.affiliation: Department of Molecular and Environmental Pathology, The University of Tokushima, Tokushima, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Bando
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.|Fujii Memorial Institute of Medical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.|Fujii Memorial Institute of Medical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan. mitsuo.shimada@tokushima-u.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D059648:Kisspeptins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9