The Relationship Between Microsatellite Instability And Hepatocyte Growth Factor And Their Influence On Survival In Colorectal Cancer

Objective:To investigate the expression of hepatocyte growth factor(HGF) and its relationship with microsatellite instability(MSI) and the influence on survival in colorectal cancer. Methods:1. Immunohistochemistry(IHC) was used to detect the expression of HGF and MSI in 98 specimens of colorectal cancer. Tumors lacking protein expression of any of the four mismatch repair genes(MLH1,PMS2,MSH2 or MSH6) were labelled as MSI,the rest were considered to be microsatellite stable(MSS).2. Associations between expression and clinicopathological factors were assessed using Chi-square tests. Kaplan–Meier curves, log-rank tests, and Cox regression were used to summarise associations between biomarker expression and overall survival.3. Immunocytochemistry(ICC)was used to detect the expression of HGF and MSI in human colorectal cancer cell line HCT-116 and HT-29.4. Western Blot was used to detect the content of protein HGF in cell line HCT-116 and HT-29.5. After treated with PHA-665752, cell growth of cell line HCT-116 and HT-29 was assessed by MTT assay. Results:1. The incidence of MSI in 98 colorectal specimens was 32.7%, and was statistically correlated with the location of tumor and differential degree(P<0.05). The HGF-expression rates were 71.4%,patients with an MSI tumor had a signifcantly higher expression of HGF,compared with patients with an MSS tumor(P=0.048).2. The 5-year survival rate of MSI group and MSS group were 39.8% and 58.7%,The difference was statistically significant(P=0.009).The 5-year survival rate of HGF-positive group and HGF-negative group were 46.2% and 67%,The difference was statistically significant(P=0.035).In multivariable analyses, both MSI and HGF are the independent prognostic factors in colorectal cancer(P=0.031 and P=0.023).3. HCT-116 is the cell line with MSI and HT-29 is with MSS.4. The content of protein HGF in cell line HCT-116 obviously higher than HT-29(P<0.05).5.The inhibitory ratio of HCT-116 is higher than HT-29(P<0.05). Conclusion:The high-expression of HGF is significantly associated with microsatellite instability in colorectal cancer, both microsatellite instability and HGF are important factors associated with patient survival in colorectal cancer.The c MET inhibitor is more effective in the treatment of human colorectal cancer cell with MSI.