Improved Method To Build Lung Cancer PDX Models By Surgical Resection Samples And Its Association With B7-H3 Expression

Objective:In this study,we improved the traditional method,evaluated the feasibility of establishing PDX models by use of surgical,we also want to explore correlation between PDXs formation and primary tumor B7-H3 protein expression.Methods:From September 2017 to July 2018,24 patients were enrolled in this study.The pathological diagnoses were as follows;15 adenocarcinomas,7 squamous cell carcinomas,1 large cell carcinoma,and 1 small cell carcinoma.The tumor tissues were cut into sizes of 2 × 2×2mm3/fragments and inoculated subcutaneously into immunodeficiency mice with trocar needle.The engrafted tumors were passaged at least 3 generations.B7-H3 IHC staining was performed on primary tumors,in order to explore correlation between PDXs formation and B7-H3 protein expression.We also performed H&E staining to evaluate whether established PDX models retained the histological features of primary tumor.Results:1.The engrafted tumors were passaged at least 3 generations as the standard of successful PDX modeling.Xenograft formation success was achieved in 19 out of 24 cases(79.2%).The time between implantation to tumor formation was an average of 81.5 days(27-154 days)in P1,while an average of 44.4 days(14-122 days)in P2 and 26.9 days(12-75 days)in P3.2.The diameter of tumor was associated with tumor engraftment,the longer the diameter,the easier to engraftment formation(P=0.0342).The data also suggested that the lung cancers with B7-H3 expression greatly induced PDX formation(P=0.0375).3.The histological characters of each passages were resembled the primary tumors.Conclusion:1.This study shows that the sample from carefully selected lung cancer by surgical resection can be used for establish PDX models with high success rates,this improved method more close to the actual clinical work.Compared with the same kind of research,the success rate of xenograft has a significant improvement,so this improved method is suitable for promotion and application.2.The results of H&E staining showed that the histological characters of each passages were resembled the primary tumors.3.The diameter of tumor was associated with tumor engraftment and higher B7-H3 expression shows statistically significant difference with PDX models formation.