Expression And Clinical Significance Of PD-L1 And PD-1 In Deficient Mismatch Repair Gene Of Colorectal Cancer

Objective investigate the expression of PD-1 and PD-L1 in deficient mismatch repair gene of colorectal cancer and its clinical significance.Method Select 279 cases of colorectal cancer from Chenzhou First People’s Hospital affiliated to University of South China during 2007-1-1 to 2010-12-31, the expression of mismatch repair protein h MLH1 and h MSH2 in colorectal cancer tumor tissues was detected by immunohistochemistry,screened in 42 cases of deficient mismatch repair gene of colorectal cancer patients as the experimental group and in the rest of the normal mismatch repair gene of colorectal carcinoma in 40 cases were randomly selected as the control group. Collected in the experimental group and the control group of 82 patients of cancer tissue and paracancerous tissue(from the outer edge of the cancer tissue 3cm) and normal intestinal mucosa tissue(from the outer edge of the cancer tissue 10cm) specimens, the expression of PD-L1 and PD-1 in the experimental group and control group was detected by immunohistochemistry too.Collected the patient’s gender, age, tumor site,T staging, tumor differentiation and N staging, UICC stage, tumor size, intravascular cancer embolus clinical and pathological data and follow-up data,useing SPSS 18.0 statistical software for statistical analysis, survival was calculated using Kaplan Meier survival curve method, survival rate between group compared with the log rank test, multivariate analysis using the Cox proportional hazards model, P<0.05 for differences were statistically significant.Result In 279 cases of colorectal cancer patients, there were 42 cases of deficient mismatch repair gene of colorectal cancer, 237 cases of normal type,The h MLH1 and h MSH2 were expressed in the nucleus,including 30 cases of h MLH1 protein expression deletion(71%), and 12 cases of h MSH2 protein expression deficiency(29%). PD-L1 was mainly localized in the colorectal cancer cells and cell membrane and cytoplasm of interstitial cells, there are two kinds of cancer mesenchymal cells, lymphocyte and macrophage. PD-1 protein was mainly localized in the cytoplasm and cell membrane of the interstitial lymphocytes.The positive expression rates of PD-L1, PD-1 protein in the experimental group and the control group in the cancer tissue were 52.4%, 30.0% and 50.0%, 25.0%, respectively, and the difference was statistically significant(P<0.05). There was no significant difference in the expression of adjacent tissues and normal tissues, The positive rates of tumor adjacent tissues in the two groups were 14.2%, 7.5% and 9.5%,5%,respectively(P>0.05).In the experimental group, the expression of tumor tissue, adjacent tissues and normal tissues was significantly different(P<0.05).The positive rate of co-expression of PD-L1 and PD-1 in cancer tissues of experimental group and the control group was 40.4% and 20%, there are differences(P<0.05), and in normal tissues and cancer adjacent tissues without significant difference(P>0.05). In mismatch repair deficient colorectal cancer tissues,PD-1 positive lymphocytes infiltration degree and cancer cells of PD-L1 expression and cancer interstitial lymphocytic PD-L1 expression correlation(P<0.05).PD-1 positive lymphocytes infiltration degree and the expression of PD-L1 in cancer cells and cancer interstitial lymphocyte is related(P<0.05). Data analysis showed that the positive expression of PD-L1 and the degree of tumor differentiation, N stage, UICC stage, vascular invasion related(P<0.05). The expression of PD-1 was correlated with N stage, UICC stage and vascular tumor thrombus(P<0.05). Co-expression of PD-1 and PD-L1 and patient gender, age, tumor site, T staging, UICC staging and the size of tumor have no association(P > 0.05),and related with the degree of tumor differentiation, N stage, lymphovascular invasion(P<0.05).Single factor analysis showed that the degree of tumor differentiation, T stage, N staging, UICC staging, vascular tumor thrombus, PD-L1, PD-1, PD-L1/PD-1 are the prognostic factors of patients with mismatch repair deficient colorectal cancer(P<0.05).Put these factors into the Cox regression model for multivariate analysis. The study shows that the independent risk factors influencing the prognosis is PD-L1(P=0.002, HR=0.084, 95%CI=0.017-0.405) and PD-L1/PD-1(P=0.006, HR=0.333, 95%CI=0.151-0.734).Conclusion1. There is a significantly different at the expression of PD-L1 and PD-1 protein in cancerous tissue of mismatch repair deficient and mismatch repair gene normal colorectal cancer,while with no difference in tumor adjacent tissue and normal tissue. 2. There is a significantly different at the expression of PD-L1 and PD-1 protein in cancerous tissue, tumor adjacent tissue and normal tissue of mismatch repair deficient colorectal cancer. 3. The expression of PD-L1 was correlated with the degree of tumor differentiation, N stage, UICC stage, and vascular tumor thrombus,and the expression of PD-1 was related to the degree of tumor differentiation, N stage, vascular tumor thrombus. 4. The degree of tumor differentiation, T stage, N staging, UICC stage, lymphovascular invasion, PD-L1, PD-1,PD-L1/PD-1 ware the prognostic factors of mismatch repair deficient colorectal cancer. 5. The positive expression of PD-L1, PD-L1/PD-1 were the independent prognostic factors of mismatch repair deficient colorectal cancer.