The Expression And Significance Of Predictive Biomarkers Of Immune Checkpoint Therapy In Gastric Cancer

Objective:This study discovered the predictive biomarkers for immune checkpoint therapy such as PD-L1,TMB and MSI and evaluated the expression of predictive biomarkers in GC.Follow up and analyze the treatment effect of 6 cases of AGC treated with Carrelizumab in order to expound the clinical significance of predictive biomarkers of immune checkpoint therapy.This study eventually aim to provide some new strategies for the immunotherapy of GC.Methods:A retrospective analysis of the clinical data of 106 patients with AGC who received systematic treatment and PD-L1,MSI,and TMB testing in the Department of Gastrointestinal Surgery of Shandong Provincial Hospital from January 2019 to March 2021.In this study,80 patients were included after inclusion and exclusion.In the research method,the expression of PD-L1 and MSI in GC tissue and the degree of positive expression were evaluated by immunohistochemistry.The PD-L1 group is grouped according to the Combined Positive Score(CPS).Patients with CPS<1 were set as PD-L1(-)group,and patients with CPS≥1 were set as PD-L1(+)group.In the PD-L1(+)group,1≤CPS<10 is the weakly positive expression subgroup+,10≤CPS<50 is the positive expression subgroup++,and CPS≥50 is the strong positive expression subgroup+++.In terms of MSI expression,grouping is based on MLH1,MSH2,MSH6 and PMS2.If there is no lack or lack of one of the above four proteins,it is set as the microsatellite stable MSS/MSI-L group,and the lack of two or more of the above four proteins is set as MSI-H group.As for TMB,the TMB values of patients were measured by Next-Generation Sequencing(NGS).Patients with TMB<10 mutations/Mb were set as the low tumor mutation burden(TMB-L)group,and patients with TMB≥10 mutations/Mb were set as the high tumor mutation burden(TMB-H)Group.Use statistical methods to analyze the differences in clinicopathological characteristics between PD-L1(-)group and PD-L1(+)group and PD-L1(+)subgroups,the difference and the relevance between PD-L1 and TMB and MSI.P<0.05 indicates that the difference is statistically.Results:1.The results of predictive biomarkers expression for immune checkpoint therapy in GC(1)PD-L1:Among the 73 patients were detected by the immunohistochemistry of PD-L1,13 patients were PD-L1(-),accounting for 17.8%,and 60 patients were PD-L1(+),accounting for 82.2%.Among PD-L1(+)patients,there were 26 patients with 10≤CPS≤50,accounting for 43.3%,and 8 patients with CPS≥50,accounting for 13.3%.(2)TMB:Among the 59 patients were tested by the Next-generation Sequencing.There were 51 patients who express TMB-L(accounting for 86.4%)and 8 patients express TMB-H(accounting for 13.6%).(3)MSI:Among the 80 patients were detected by immunohistochemistry of MLH1 MSH2、MSH6 and PMS2.There were 78 patients who did not express MSI-H,(accounting for 97.5%)and 2 patients expressed MSI-H(accounting for 2.5%).2.The difference and correlation analysis of PD-L1(-)group and PD-L1(+)group in TMB and MSI.There is neither difference nor correlation between the two groups in terms of TMB and MSI by the statistical analysis.3.The difference analysis of clinicopathological characteristics between PD-L1(-)group and PD-L1(+)groupThe two groups had statistical differences in BMI and TNM staging by the statistical analysis.Compared with lean GC patients,PD-L1 seems to be more likely to be expressed in overweight and obese GC patients.Compared with PD-L1(-)GC patients,PD-L1(+)gastric cancer patients have a late clinicopathological stage and a high degree of tumor malignancy.4.The difference analysis of clinicopathological characteristics of PD-L1 positive subgroups(+,++,+++)The PD-L1 positive subgroups(+,++,+++)did not have statistical differences in clinicopathological characteristics by the statistical analysis.5.Analysis of curative effect of 6 cases of advanced GC treated with Carrelizumab(1)After follow-up and statistical analysis,it was found that PD-L1(-)AGC patients treated with Carrelizumab is less effective.(2)For patients with PD-L1(+)AGC,preoperative treatment of combination medication including Carrelizumab may increase the surgical resection rate,control the tumor progression,increase the cure rate and improve the prognosis.(3)For patients with PD-L1(+)AGC,postoperative treatment of combination medication including Carrelizumab can significantly prolong the progression-free survival of patients.Conclusions:PD-L1 can be used as a predictive biomarker for the evaluation of the efficacy of ICIs,providing strategies for selecting the appropriate population to apply ICIs and maximizing the therapeutic effect.ICIs can be used as one of the main drugs of choice for the perioperative treatment of AGC.Using the ICIs to PD-L1(+)AGC can increase the surgical resection rate,control the tumor progression,increase the cure rate,improve the prognosis and prolong the survival.