| ?Background?Colorectal carcinoma has become one of the leading causes of carcinoma related death in the world in recent years.Colorectal carcinoma is one of the most common digestive malignant tumors in human beings.China is one of the countries with high incidence of colorectal carcinoma.With the change of diet structure and living environment,the incidence is increasing year by year,and the recurrence and metastasis after operation is not optimistic.The 5 year survival rate is 50-60%.The occurrence of colorectal carcinoma,the development of multiple factors in different stages,multiple genetic changes result from the normal intestinal mucosa,tubular adenoma,colorectal carcinoma gradually formed the development process,and the activation of oncogene and inactivation of tumor suppressor genes,cell signal transduction system disorder,uncontrolled proliferation and apoptosis of tumor cells is closely related to it.In recent years,epidemiological studies have shown that the incidence of colorectal carcinoma in China is increasing gradually year by year,and about 20%~25% patients were diagnosed in the late stage,which is a serious threat to life safety.Surgical treatment and chemotherapy are still the main means of treatment for colorectal carcinoma.In colorectal carcinomas,there are standard chemotherapy programs in the world,and the application of molecular targeted drugs has also achieved good results.However,now that our country is still a developing country,carcinoma patients economic conditions are not so good,molecular targeted therapy application rate is not high,the medical treatment with chemotherapy is still the main treatment.In addition,the side effects of surgery,chemotherapy and radiotherapy seriously affect the prognosis of patients and reduce the quality of life of patients.Immunotherapy is a new method to treat solid tumors.In this new field,immunoassay sites as negative regulators in the immune system play an important role in the field of anti-tumor immune response.Therefore,immunological examination site blocking factors,such as resistance to cytotoxic T lymphocyte associated antigen 4(CTLA-4),PD-1,PD-L1,have now been developed for antitumor drugs that have promising results in preclinical and clinical studies.A blocking PD-1and PD-L1 pre-clinical test results are full of hope,especially in those with microsatellite instability(MSI)is more obvious in patients with colorectal carcinoma.Some researchers will confirm these preliminary results in further in-depth clinical trials.The feasibility of the combined therapy and the identification of the effects of the two biomarkers as immunoassay site blockers are also evaluated in which populations are more likely to benefit or resist them.The existing research focused on some specific genes to chemotherapy have guiding significance,but genetic testing cost is higher,and the expression of immunohistochemical staining method to detect PD-1and PD-L1 in colorectal carcinoma,will help us choose immune therapy to treat patients with colorectal carcinoma,and the cost of studying the pathological parameters is relatively low,domestic studies have reported special significance of clinical pathological parameters in other solid tumors.Ki-67 is often used to reflect the degree of cell proliferation,which is of great significance in the differential diagnosis of some benign and malignant lesions.Therefore,this study collected colorectal carcinoma tissues by immunohistochemical technique to detect the expression of PD-1 and PD-L1 in colorectal carcinoma,and investigate the significance in the diagnosis of colorectal carcinoma and the relationship with clinicopathological parameters and tumor proliferation ability.?purpose?1.To detect the expression of PD-1 and PD-L1 in colorectal carcinoma,and discuss its relationship with clinicopathological features and clinical stages,and explore its significance in the occurrence and progression of colorectal carcinoma.2.To observe the PD-L1 expression sites and features in colorectal carcinoma cell lines.3.To investigate the expression of PD-L1 positive overall survival of patients with colorectal carcinoma,and the possible relationship between them.?Methods?1.The expression of PD-1 and PD-L1 in colorectal carcinoma and tubular adenoma was detected by immunohistochemistry.2.The expression of the protein of PD-L1 in colorectal carcinoma cell lines(HCT116,Lo Vo,SW480 and SW620)was detected by Western blot.3.The expression of PD-L1 protein in colorectal carcinoma cell lines(HCT116,Lo Vo,SW480 and SW620)was detected by immunofluorescence.4.The expression of PD-L1 protein in colorectal carcinoma cell lines(HCT116,Lo Vo,SW480 and SW620)was detected by cell immunohistochemical method.5.The survival time of the colorectal patients in this study was followed up and the possible correlation between the expression of PD-L1 and the total survival time of the patients was analyzed.?Results?1.In group of the PD-L1 expression tissues,102 cases were positive in low middle differentiation group and 34 cases were negative,29 cases were positive in senior management group and 37 cases were negative,the difference was statistically significant(p=0.0001).63 cases were positive in colon carcinoma,31 were negative,67 were positive in rectal carcinoma,39 were negative,there was no significant difference(p=0.573).There were 75 cases of ulcer type,25 cases of negative,55 cases of non-ulcer type and 45 negative cases;the difference was statistically significant(p=0.018).There were 2 cases of infiltration type positive,8 cases negative,128 cases of non invasive positive and 62 cases negative,the difference was statistically significant(p=0.019).The depth of invasion was positive in the muscularis propria,13 cases were negative,and15 cases were negative.The depth of invasion was higher than that of the muscularis propria,127 cases were positive,and 45 cases were negative.The difference was statistically significant(p=0.003).Patients without lymph node metastasis were positive in 84 cases,46 cases were negative;lymph node metastasis in patients with 46 positive cases,24 cases were negative;there was no statistically significant difference(p = 1).2.In the tissue wax of PD-1,92 cases were positive and 108 cases were negative.In colorectal cancer,49 cases were positive,45 cases were negative,and 43 cases were positive and 63 cases were negative in rectal cancer,the difference was statistically significant(p=0.015).In the Ki-67< 70%,57 cases was positive,70 cases was negative;in the Ki-67?70%,15 cases was positive,58 cases was negative,the difference was statistically significant(p=0.001).3.In the tissue wax blocks of the same tissue wax mass with both pd-l1 and pd-1 positive expression,there were significant differences between the degree of differentiation and grade of tumor and the size of tumor observed by naked eye.The difference was statistically significant(p< 0.05).?Conclusions?1.PD-L1 and PD-1 are expressed in colorectal carcinoma tissues,and the expression of PD-L1 in tumor cells may be a potential target of biological immunotherapy for colorectal carcinomas.2.The expression of PD-L1 protein in Lo Vo cells is the highest,and this cell line may be a good cell model for further study on biological immunotherapy of human colorectal carcinoma in vitro experiment.3.The survival time of colorectal carcinoma patients who expressed PD-L1 is shorter than that of colorectal carcinoma patients who do not express PD-L1.The expression of PD-L1 in tumor is expected to be one of the predictors of prognosis for colorectal carcinomas. |
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