Expression And Clinical Significance Of MTH1 In Advanced Gastric Cancer

OBJECTIVE:The study aimed to investigate the expression of MTH1 in advanced gastric cancer(AGC) and the prognosis value of MTH1 in AGC.Meanwhile,we evaluated the relationship between the expression of MTH1 and the clinical pathological features in AGC. METHORD:125 AGC patients who received chemotherapy in Tianjin Medical University Cancer Institute and hospital from January 2008 to December 2012 were included in our study. All of these cases were unresectable and can benefit only from palliative treatment.They received at least 2 cycle oxaliplatin-based chemotherapy.The immunohistochemistry was employed to detect the expression of MTH1 in tissue specimen of 125 patients. The expression of MTH1 in normal gastric mucosal tissue were also detected.We employed the chi-square test to analysis the relationship between the expression of MTH1 and the clinical pathological features in AGC,including the gender,age of the patients, the size,location and differentiation of the original tumor. Kaplan-Meier method and Log-rank test were performed to explore the correlation between MTH1 expression and survival. The Cox regression analysis was used to evaluate the connection between expression of MTH1 and prognosis of AGCpatient. Further, chi-square test was explored to detected the connection between MTH1 expression and the disease control rate and the objective response rate.. RESULT:Cytoplasm and nuclear staining on the tissue specimen of gastric carcinoma is observed,especially in the cytoplasm.The desmoplastic stroma surrounding the tumor cells were negatively expressed.Among the 125 cases, The positive rate of MTH1 was 52%(65/125),which was significantly higher than normal gastric mucosal tissue 20%(4/20),χ2= 7.079, P=0.008. However,there was no significant correlation between the expression of MTH1 and age,gender,the size of tumor, differentiation,location of tumor(P>0.05).In the MTH1 positive group,the median PFS was 4.83 months.The median PFS of MTH1-negetive patients was 6.27 months(χ2= 5.973,P=0.019).The median OS was 8.27 in the MTH1 positive group, whereas the median OS of MTH1-negetive was 13.53 months(χ2= 11.794,P=0.001). The disease control rate of MTH1-positive patients was significantly worse than MTH1-negative patients(56% vs. 73%,χ2=4.363,P=0.037).Among 111 patients who had measurable disease,the objective response rate between MTH1-positive group and MTH1-negative group were 20.69% and36.54%(χ2=3.403,P=0.065)Further multivariate analysis suggested that differentiation of the original tumor, the location of original tumor,CEA and the expression of MTH1 were dependent prognosis factors. CONCLUSION:In gastric carcinoma, MTH1 was highly expressed.The expression of MTH1 is correlated with the survival time of AGC,the MTH1 positive patients tended to have a poor prognosis.At the same time,the expression of MTH1 maybe an indicator of the chemosensitivity, the MTH1 positive patients tended to have a better response to chemotherapy.Further study is needed to validate the conclusion..MTH1 may be a promising indicator to predict the outcome of AGC patients.