Expressions and significances of Kiss-1 and matrix metalloproteinases-9 proteins in the colorectal cancer tissues of patients with synchronous colorectal liver metastasis / 中华消化外科杂志

ABSTRACT

Objective To investigate the expressions and correlations of Kiss-1 and matrix metalloproteinases-9 (MMP9) proteins in the colorectal cancer (CRC) tissues of patients with synchronous colorectal liver metastasis (SCRLM),and the association with the clinicopathologic factors and prognosis of patients.Methods The retrospective case-control study was adopted.The clinicopathological data of 96 patients with SCRLM and 69 patients with CRC and no metastasis who were admitted to the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University from January 2000 to May 2013 were collected.The 96 CRC tissues and 50 adjacent normal tissues (distance from resection margin ≥ 5 cm) were collected from 96 patients with SCRLM,and 69 CRC tissues were collected from 69 patients with CRC and no metastasis.Expressions of Kiss-1 and MMP9 protein were detected by immunohistochemistry (IHC).The follow-up of outpatient examination and telephone interview was performed to detect survival of patients till August 2014.Comparison of count data and correlation between expressions of Kiss-1 or MMP9 protein and clinicopathological factors were analyzed by the chi-square test and Fisher exact probability.Survival curve was drawn using the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Correlation analysis was done by the Pearson correlation.Results Expression of Kiss-1 protein was located in the cytoplasm of tissue cells.The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 24.0％ (23/96),43.5％ (30/69) and 52.0％ (26/50),respectively,with a significant difference among the 3 tissues (x2 =14.307,P ＜ 0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2 =0.845,P ＞ 0.05).The positive expression rate of Kiss-1 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =0.702,11.594,P ＜ 0.05).Expression of MMP9 protein was located in the cytoplasm of tissue cells.The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM and with CRC and no metastasis and in adjacent normal tissues were 67.7 ％ (65/96),62.3 ％ (43/69) and 36.0％ (18/50),respectively,with a significant difference among the 3 tissues (x2=14.203,P ＜0.05) and no significant difference between CRC tissues of patients with CRC and no metastasis and patients with SCRLM (x2=8.038,P ＞ 0.05).The positive expression rate of MMP9 protein in CRC tissues of patients with SCRLM was significantly different from that in CRC tissues of patients with CRC and no metastasis and in adjacent normal tissues (x2 =13.475,13.475,P ＜ 0.05).The positive expression rates of Kiss-1 protein in CRC tissues of patients with SCRLM were 66.7％,21.9％ and 17.6％ in the high-,mederate-and low-differentiated tumor,50.0％,28.6％ and 17.5％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 16.9％ in patients with and without lymph node metastasis,respectively,showing significant differences among the tumor differentiation degree,depth of tumor invasion and lymph node metastasis (x2=6.546,6.172,7.453,P ＜0.05).The positive expression rates of MMP9 protein in CRC tissues of patients with SCRLM were 25.0％,66.7％ and 76.2％ in the muscular layer of tumor invasion,outside of serosa and serosal layer,44.0％ and 76.1％ in patients with and without lymph node metastasis,respectively,showing significant differences between the depth of tumor invasion and lymph node metastasis (x2 =12.094,8.690,P ＜ 0.05).All the 96 patients with SCRLM were followed up for a median time of 68 months (range,12-176 months).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,26 months,69.6％ and 26.1％ in patients with SCRLM and positive expression of Kiss-1 protein and 26 months,19 months,24.7％ and 12.3％ in patients with SCRLM and negative expression of Kiss-1 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=16.578,14.436,P ＜ 0.05).The median overall survival time,median tumor-free survival time,5-year cumulative survival rate and 5-year tumor-free survival rate were 31 months,19 months,24.6％ and 12.3％ in patients with SCRLM and positive expression of MMP9 protein and 28 months,16 months,58.1％ and 22.6％ in patients with SCRLM and negative expression of MMP9 protein,respectively,showing significant differences between the overall survival and tumor-free survival (x2=14.073,8.532,P ＜0.05).Of 96 patients with SCRLM,there were 23 patients with positive expression of Kiss-1 protein (10 with positive expression of MMP9 protein and 13 with negative expression of MMP9 protein) and 73 with negative expression of Kiss-1 protein (55 with positive expression of MMP9 protein and 18 with negative expression of MMP9 protein),with a negative correlation between expressions of Kiss-1 protein and MMP9 protein (r =-0.291,P ＜ 0.05).Conclusions The reduced expression of Kiss-1 protein and elevated expression of MMP9 protein are closely associated with invasion and metastasis of CRC and prognosis of patients.A combination detection of Kiss-1 and MMP9 proteins is expected to become a marker for predicting the prognosis of patients with SCRLM based on the negative correlation between them.