Chengzhan Zhu1,2, Chie Takasu1, Yuji Morine1, Yoshimi Bando3, Tetsuya Ikemoto1, Yu Saito1,2, Shinichiro Yamada1,2, Satoru Imura1, Yusuke Arakawa1, Mitsuo Shimada4. 1. Department of Surgery, The University of Tokushima, Tokushima, Japan. 2. Fujii Memorial Institute of Medical Sciences, The University of Tokushima, Tokushima, Japan. 3. Department of Molecular and Environmental Pathology, The University of Tokushima, Tokushima, Japan. 4. Department of Surgery, The University of Tokushima, Tokushima, Japan. mitsuo.shimada@tokushima-u.ac.jp.
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. CONCLUSION: KISS1 could be a promising prognostic and therapeutic marker in CRLM. KISS1 low expression may induce high MMP-9 expression in neutrophils.
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. CONCLUSION:KISS1 could be a promising prognostic and therapeutic marker in CRLM. KISS1 low expression may induce high MMP-9 expression in neutrophils.