EGFR野生型非小细胞肺癌中CD44对PD-L1的调控作用研究OA

Objective This project primarily investigated the regulation of CD44 on PD-L1 in EGFR wild-type Non-small cell lung cancer(NSCLC),and revealed the potential molecular mechanism of the process,aiming to identify a novel target for targeted therapy and cancer immunotherapy of EGFR wild-type NSCLC.Methods 1.Bioinformatics analysis was employed in conjunction with TCGA database for data retrieval and analysis to investigate the association between CD44 and PD-L1 expression in EGFR wild-type NSCLC,as well as the survival rate analysis of patients with high co-expression of both.2.Human EGFR wild-type NSCLC cell lines(H1299,H460,A549)were cultured in vitro.Flow cytometry,qPCR and western-blot were utilized to assess the impact of CD44 knockdown or overexpression on the positive cell population ratio,mRNA and protein expression levels of PD-L1 in EGFR wild-type NSCLC cells.3.GraphPad Prism software(v9)was used for statistical analysis and graph creation.Quantitative data are presented as mean±standard deviation(Mean±SD),and intergroup differences were analyzed by unpaired t-test.Results Bioinformatics analy-sis showed a significant positive correlation between CD44 expression and PD-L1 expression levels in EGFR wild-type NSCLC(Lung Adenocarcinoma:P<0.05,R=0.54;Lung squamous cell carcinoma:P<0.05,R=0.19).Moreover,the high expression level of CD44 and PD-L1 is associated with decreased overall survival of NSCLC patients when compared with CD44 and PD-L1 negative patients(HR=0.65,95%CI:1.57～2.57,P=0.023).In H1299,H460 and A549 cells,the proportion of positive cell populations,mRNA and protein expression levels of PD-L1 were significantly decreased after CD44 knockdown(P<0.05).After CD44 overexpres-sion,the mRNA and protein expression levels of PD-L1 in H1299 and H460 cells were increased(P<0.05).Conclusion CD44 in EGFR wild-type NSCLC cells has a positive regulatory effect on PD-L1,and the co-high expression of both is associated with a poor prognosis of lung cancer.