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Clinical Study On The Correlation Between CD38 Antigen Expression And Drug Resistance Of PD-1 Inhibitor Therapy In Non-Small Cell Lung Cancer

Posted on:2023-09-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y W WangFull Text:PDF
GTID:2544306845971829Subject:Internal Medicine
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Part 1 Study on the expression of CD38 in lung cancer tissues Objective:To explore the expression level of CD38 in lung cancer tissue,paratumor tissue and normal lung tissue of patients with non-small cell lung cancer and the correlation between CD38 expression level and patient age,gender,pathological type and PD-L1,and to explore the relationship between CD38 expression level and immune checkpoints Relationship between inhibitor efficacy.Methods: 55 patients with non-small cell lung cancer who were admitted to the Department of Medical Oncology from 2019.12 to 2021.12 were collected,and the expression levels of CD38 and PD-L1 in tumor tissues were detected by immunohistochemistry(IHC).level,with 25% of positive cells as the critical value.Statistical analysis method,combined with clinicopathological parameters and follow-up data,was used to analyze the difference of CD38 expression level in different tissues and the correlation between the expression level in tumor tissue and the clinical characteristics and PD-L1 expression level of patients.Results: Fifty-five patient samples were collected,and the differences in CD38 expression levels in tumor tissue,paratumor tissue,and normal lung tissue samples were compared.The analysis results showed that the expression level of CD38 in tumor tissue was significantly different from that in adjacent tissue(P=0.036),and was significantly different from that in normal tissue(P=0.005).There was no significant statistical difference between them(P=0.482).Statistical analysis showed that the expression level of CD38 in tumor tissue was statistically correlated with the patient’s age(P=0.024),but not with the patient’s gender,pathological type and PD-L1 expression level(P1=0.544,P2=0.090).,P3=0.915).Conclusion: 1.The expression level of CD38 in tumor tissue was significantly higher than that in paratumor tissue and normal lung tissue;2.The expression level of CD38 is correlated with age,but has no significant correlation with gender,pathological type and PD-L1 expression level;Part Ⅱ: The relationship between CD38 expression level and PD-1 antibody treatment resistance Objective: To monitor whether CD38 expression in immunotherapy is a relevant factor in tumor resistance to PD-1 blockade therapy,and to explore whether CD38 antigen expression can be used as a predictor of immunotherapy benefit.Methods: After screening in the previous part of the experiment,a total of 41 patients who were hospitalized with PD-1 inhibitors in the medical oncology department were collected,and the patients were given PD-1 inhibitors combined with chemotherapy.The peripheral blood samples of the patients during the treatment were collected and detected by ELISA kits.The dynamic expression of CD38 in blood,at the same time,western blotting and PCR methods were used to further determine the expression at the protein level and RNA level,and the efficacy was evaluated on time until the drug resistance progressed.The CD38 expression levels in different treatment periods were compared to determine whether there was a difference through statistical analysis..Combined with the immunohistochemical results of the first part of the tumor tissue,taking the proportion of positive cells as the critical value of 25%,the patients were divided into a CD38 high expression group and a low expression group,and the relationship between the CD38 expression level and the progression-free survival(PFS)of the patients was analyzed.relationship,to explore whether there is consistency in tissue and blood samples.Results:During the course of immunotherapy,the expression level of serum CD38 at the time of drug resistance,the average expression level during the medication interval and the expression level before the start of treatment were all significantly different among the three groups(P1=0.001,P2=0.001,P3=0.005)..The positive cells in the tumor tissue were grouped by 25% as the critical value,among which 27 were in the high expression group of CD38 and 14 in the low expression group.The median PFS of the high expression group was 9.6 months,and the median PFS of the low expression group was 11.25 months.After statistical analysis,the difference in progression-free survival between the two groups was statistically significant(P=0.014).There was no statistical correlation between the expression of CD38 in tumor tissue and serum(P=0.425).Conclusion: 1.The high expression level of CD38 is associated with immune resistance in PD-1 inhibitor therapy;2.The overall PFS of the high CD38 expression group in tumor tissue was shorter(9.6 VS 11.25).
Keywords/Search Tags:Non-small cell lung cancer, CD38, PD-1 inhibitor therapy, Predictive markers
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