Expression Of STING And PD-L1 In Colorectal Cancer And Their Correlation With Clinical Prognosis

Background Colorectal cancer is the third most common malignancy in terms of morbidity and the fourth in mortality in worldwide.The latest data show that the incidence and mortality of colorectal cancer in China is increasing year by year.Immunotherapy has opened up a new therapeutic prospect in the field of tumor therapy,and has become the most important treatment method after surgery,radiotherapy,chemotherapy and targeted therapy.Studies have shown that PD-1/PD-L1(programmed death receptor-1/programmed death ligand-1) can negatively regulate the immune response by inhibiting the activation and proliferation of T cells,and it also can participate in regulating of immune tolerance,microbial infection and of tumor cells immune escape.STING(stimulator of interferon genes)causes the production of type I IFN in the tumor microenvironment,and promotes the production of tumor antigen specific CD8+T cells via dendritic cells,thereby enhancing the role of tumor inhibition.Studies have shown that STING down-regulation can reduce the pd-l1 upregulation induced by cisplatin.STING agonist combined with pd-1antibody has synergistic and synergistic anti-tumor effect,indicating that STING and pd-l1 have some unknown relationship.The clinical correlation between the two expressions in tumors,especially colorectal cancer,has not been reported.In this study,the expression levels of pd-l1 and STING in colorectal cancer and corresponding paracancer tissues were detected by immunohistochemistry,and the relationship between them and clinicopathological characteristics was analyzed to explore the correlation between their expression in colorectal cancer and their relationship with the prognosis,so as to provide some experimental references for the prognosis evaluation of clinical colorectal cancer patients.Objective To investigate the expression of PD-L1 and STING in colorectal cancer and analyze their correlation with disease prognosis.Methods The colorectal tissue chip was taken as the research object.Immunohistochemical methods were used to detect expression of PD-L1 and STING of 87 cases of colorectal cancer tissue and corresponding adjacent tissue in the tissue chip.Chi-square test or Fisher's test were used to analyze the relationship of expression of PD-L1 and STING and with the clinical pathological features.Kaplan-Meier curves were used to analyze the relationship between expression of PD-L1 and STING and the prognosis of colorectal cancer.Results The positive expression rate of PD-L1 in 87 cases of colorectal cancer tissue and corresponding adjacent tissue was 79.3% and 42.5% respectively,and the difference was signifcant(P<0.05).The positive expression rate of PD-L1 in colorectal carcinoma tissues was related with differentiation(P<0.05),but not associated with age,gender,tumor size,differentiation,TNM clinical stage,or depth of invasion(P>0.05).The positive expression rate of STING in 87 cases colorectal cancer tissues and corresponding adjacent tissue was 9.2% and 40.2%respectively and the difference was signifcant(P<0.05).The positive expression rate of STING in colorectal carcinoma tissue was correlated with gender and age(P<0.05),but not associated with tumor size,differentiation,depth of invasion,and TNM clinical stage(P>0.05).The expression rate of PD-L1 was related to the prognosis of colorectal cancer(P=0.018).The expression rate of STING was not correlated with prognosis of colorectal cancer(P=0.784).In four independent groups(PD-L1~+STING~+ group,PD-L1~-STING~-group,PD-L1~-STING~+group,PD-L1~+STING~-group),there were signifcant differences in 5-year survival(P=0.047<0.05),the 5-year survival rate of the PD-L1~-STING~+ group was signifcantly higher than that of the other three groups.In the STING positive group,the PD-L1~+STING~+ group had a worse prognosis than the PD-L1~-STING~+ group.In the STING negative group,the PD-L1~-STING~- group had a higher survival rate than the PD-L1~+STING~- group.Conclusion PD-L1 might promote the occurrence of tumors,STING might play an important role in antitumor immunity.PD-L1 was correlated with the prognosis of patients with colorectal cancer but the expression of STING was not obviously associated with the prognosis.Survival rates of patients with colorectal cancer were higher in patients with PD-L1 negative expression or STING positive expression.When PD-L1 expression was negative and STING expression was positive,the 5-year survival rate of patients with colorectal cancer was highest.