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Long-term Use Of Aspirin Before Diagnosis On COX-2,PD-1/PD-L1 Expression And Analysis Of Prognostic Factors In Patients With Esophageal Squamous Cell Carcinoma

Posted on:2023-10-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:J JiangFull Text:PDF
GTID:1524306818953909Subject:Surgery
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Part One Effects of long-term aspirin use before diagnosis on survival in esophageal squamous cell carcinomaObjective:Esophageal cancer(EC)is the most common lesion in the esophagus,the onset of EC is mild and short,which is therefore more likely to be ignored.Aspirin has a preventive effect on malignant tumors,and long-term low-dose aspirin use can prevent the occurrence of cancer.Methods:A retrospective study was conducted on patients who had been hospitalized in the 4th Hospital of Hebei Medical University.The chi-square test was used to compare clinico-pathological data,and the K-M curve was used to analyze these survival data and of patients taking long-term aspirin to find those meaningful predictors of survival.Results:All patients’(2310 in total)clinic-pathological data and follow-up data were analyzed,and the five-year survival rate after operation was 52.2%,hypertension(HR,1.207,95%CI,1.037-1.406,p=0.015),diabetes(HR,1.318,95%CI,1.007-1.725,p=0.044),T stage(HR,1.323,95%CI,1.177-1.487,p=0.000),N stage(HR,1.265,95%CI,1.097-1.459,p=0.001),LNR(HR,1.253,95%CI,1.021-1.535,p=0.031)and R1(HR,1.327,95%CI,1.041-1.692,p=0.022)were independent risk factors for OS,the only independent risk factor for DFS was N stage(HR,1.267,95%CI,1.051-1.527,p=0.013).Long-term use of aspirin before diagnosis had an adverse effect on postoperative OS in ESCC patients(p=0.025),but was not associated with DFS.Conclusions:For resectable esophageal cancer,hypertension,diabetes,tumor pathology,T stage,N stage and positive margin are independent risk factors for OS,and N stage is the only independent risk factor for DFS.Long-term regular use of aspirin before diagnosis adversely affects postoperative OS but not DFS in ESCC patients.Part Two Effect of long-term regular use of aspirin before diagnosis on COX-2 expression in esophageal squamous cell carcinoma and the analysis of prognostic factorsObjective: To determine the effect of long-term use of aspirin before diagnosis on COX-2 expression in patients with esophageal squamous cell carcinoma(ESCC)and whether there is a significant difference in survival between patients with different COX-2 expression.Methods: We conducted a retrospective cohort study on patients who were previously hospitalized in our hospital.A total of 2310 patients who underwent esophagectomy from January 2008 to June 2018 were followed up,of which IHC was performed for 162 patients including 79 aspirin users and 81 non-users.The K-M curve was used to analyze the cancer-specific survival rate and disease-free survival rate,and to explore the effect of taking aspirin before diagnosis on the survival rate of patients with esophageal squamous cell carcinoma(ESCC).Results: Survival analysis showed that aspirin had an effect on the expression of COX-2 in ESCC patients,and the survival of patients with negative COX-2 expression was better than that of patients with positive COX-2 expression(P<0.001).Analyzing the independent risk factors of patients taking aspirin,it was found that only T stage(HR,2.119,95%CI,1.405-3.197,P<0.001)was the independent risk factor of survival.Conclusions: 1.Long-term regular use of aspirin before diagnosis has an effect on COX-2 in ESCC patients.Patients with different COX-2 expression have significant differences in postoperative survival time.Patients who have never used aspirin and whose expression is negative have better survival time.2.The depth of tumor invasion(T stage)is the independent risk factor for postoperative survival in ESCC patients who have taken aspirin for a long time before diagnosis,and can be used as a predictor of survival.Part Three Effects of long-term use of aspirin before diagnosis on PD-1/ PD-L1 expression in esophageal squamous cell carcinomaObjective: In recent years,immunotherapy of malignant tumors has been a breakthrough in tumor treatment.PD-1/PD-L1 is one of the most widely studied immune checkpoints.Aspirin is considered to play a certain role in the immunotherapy of malignant tumors.。Methods: We performed immunohistochemical staining on a total of 138 patients in hospitalized patients,including 69 aspirin users and 69 non-users.The χ2 test was used to confirm the relationship between the use of aspirin and PD-1/PD-L1 expression before diagnosis,as well as the relationship between the expression and clinicopathological data.The KM curve was used to analyze the expression of PD-1/PD-L1 and cancer-specific survival and disease-free survival,to explore the effect of PD-1/PD-L1 expression on the survival of patients with ESCC.Results: It was found that there was no significant difference between long-term low-dose aspirin and PD-1/PD-L1 expression before diagnosis.The positive expression rate of PD-L1 in the aspirin group was slightly higher than that of the no use group,but the difference was not statistically significant(p>0.005).Different tumor differentiations had significant differences in PD-1 expression(p=0.004),and different tumor locations had significant differences in PD-L1 expression(p=0.021).Survival analysis found the expression of PD-1 has no significant effect on the survival rate and recurrence rate of ESCC patients(p>0.005).The expression of PD-L1 has an effect on the survival rate(p<0.005),but has no significant effect on the recurrence rate(p>0.005).The expression of PD-1/PD-L1 in the aspirin group had a significant effect on survival(p<0.005),but had no significant effect on disease-free survival(p>0.05).Conclusions: 1.Long-term regular use of aspirin before diagnosis has no significant effect on the expression of PD-1 and PD-L1 in ESCC patients.2.The expression of PD-1/PD-L1 in ESCC has predictive significance for the survival rate and disease-free survival rate of patients.The survival rate of negative expression is higher,the survival rate of positive expression is lower,patients with positive expression and taking aspirin before diagnosis had the worst survival,and PD-1 and PD-L1 patients with both expression have the worst survival rate.3.PD-1 is related to different tumor differentiation,PD-L1 is related to different tumor locations.
Keywords/Search Tags:Esophageal cancer, Survival analysis, Overall survival, Disease free survival, Independent risk factor, Aspirin, Esophageal squamous cell carcinoma, COX-2 expression, Independent risk factors, ESCC, Immune checkpoint, PD-1/PD–L1, Prognosis
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