Establishment And Identification Of Patient-derived Tumor Xenografts For Esophageal Carcinoma

Background and objective:Esophageal cancer is one of the common malignant tumors of the digestive tract that is harmful to human health worldwide.Due to the heterogeneity of tumor cells,their sensitivity to chemotherapeutic drugs is quite different,and the experience of chemotherapy is prone to drug resistance in some patients,which may delay the optimal timing of tumor treatment.As a representative of the in vivo model,the human-derived tumor xenograft(PDX)overcomes the defects of the tumor cell model to some extent.This study improved the PDX tumor formation rate and clinical conversion rate by improving the technical process and using humanized mice to construct an esophageal tumor animal model to more realistically simulate the tumor immune microenvironment in humans;by analyzing primary tumors and transplantation The similarities and differences between tumors in histopathology,molecular biology and genomics,to assess whether PDX retains the biological information of primary tumors,thus providing a reliable preclinical model for the study of esophageal cancer,and individualized treatment for patients and Drug screening provides an effective means.Methods:36 esophageal cancer resected tissues were transplanted subcutaneously into humanized mice.When the transplanted tumors grew to 500-1000 mm~3,they were serially inoculated into humanized mice subcutaneously until the fourth passage(P4),and the tumor tissues were collected.some were continuously passaged,and some were stored in a liquid nitrogen tank for subsequent model recovery and reestablishment,and the remaining tissues were used for HE staining,IHC staining and genes detection.The feasibility and stability of the model were verified by analyzing the pathological and genomic differences between the original tumor tissue and the PDX model tissue.Results:36 esophageal cancer tissues were resected and passaged,and 25 PDX models were established successfully.The rate of tumor formation was 69.44%.The frozen xenografts of the patients were transplanted into the subcutaneous tissue of humanized mice after resuscitation,and 23 tumor tissues were successfully grown and the rate of resuscitation was 92.0%.These xenograft models are basically consistent in histomorphology and genomics.The pathological type and risk of recurrence of esophageal cancer are correlated with the rate of tumor formation.Conclusion:This study used humanized mice to establish PDX models of esophageal cancer,which increased the rate of tumor formation.At the same time,the model basically retained the biocharacteristics and immune microenvironment of esophageal cancer.Resuscitation modeling experiments of frozen xenograft suggest that the model has a sustainable application.The pathological type of esophageal cancer and the risk of recurrence may be factors influencing the rate.