B7-H3 As A Predictor Of Clinical Outcome In Lung Adenocarcinoma Patients Treated With EGFR Tyrosine Kinase Inhibitors

Objectives1.To investigate the effect of different levels of B7-H3 expression on the response rate of EGFR-TKI targeted therapy in lung adenocarcinoma patients.2.To investigate the correlation between common signaling molecule B7-H3 and acquired drug resistance in targeted therapy of lung adenocarcinoma（EGFR-TKI）Methods1.Immunohistochemical method was used to detect B7-H3 expression in 56 lung adenocarcinoma patients,and it was divided into low and high expression level,and the relationship between high/low expression of B7-H3 and the clinical outcome of first-line anti-EGFR treatment was analyzed.The primary criteria were overall response rate（ORR）,disease control rate（DCR）and progression-free survival（PFS）,while the secondary criteria were overall survival rate（OS）.2.According to the immunohistochemical results,the proportion and occurrence time of acquired drug resistance after EGFR-TKI targeted therapy were compared between the two groups with high/low B7-H3 expression.Gefitinib-resistant EGFR mutant lung adenocarcinoma cell lines H3255 and HCC827 were induced and cultured in vitro.The wild-type cell lines were used as control,and the expression level of resistant CELL lines B7-H3 was analyzed by flow cytometry.Results1.In the subgroups with high and low B7-H3 expression,ORR was 16.0%（4/25）and74.2%（23/31）（P<0.001）,DCR was 36.0%（9/25）and 87.1%（27/31）（P<0.001）,respectively.PFS with high B7-H3 [median 8.7,95% confidence interval（CI）: 4.0-13.4]were significantly lower than PFS with low B7-H3（median not reached）[HR6.54（95%CI2.18-19.60）,P =0.001].The median OS of high B7-H3 expression was 15.9months（95%CI: 10.0-21.8）,and that of low B7-H3 expression was 25.7 months（95%CI: 9.0-42.4）[HR2.08（95%CI1.07-4.02）,P=0.03].2.In 56 lung adenocarcinoma patients,31 cases and 25 cases had low and high B7-H3 expression,respectively.By the end of observation time of this study,the cases of acquired drug resistance in patients with low and high B7-H3 expression were 12 cases（38.7%）and 14 cases（56.0%）（P=0.19,?2=1.663）,and the median drug resistance time was 13.2 months and 5.1 months（P=0.004,t=3.193）,respectively.Compared with wild-type H3255 and HCC827 cell lines,the expression level of drug-resistant strain B7-H3 was further increased.Conclusions1.B7-H3 can be used as a predictor of clinical prognosis in lung adenocarcinoma patients treated with EGFR mutation and first-line EGFR-TKIS.2.The expression level of B7-H3 is related to the acquired drug resistance of EGFR-TKI targeted therapy in lung adenocarcinoma.