Establishment And Identification Of PDX Mouse Model Of Gynecological Malignant Tumor

Objective: Cervical cancer(CC),endometrial cancer(EC)and ovarian cancer(OC),three major gynecological malignancies,seriously endanger women's physical and mental health.PDX is a powerful tool because of its predictive value and the ability to retain the characteristics of primary tumor.It is a suitable preclinical model to evaluate drug sensitivity.The purpose of this study is to construct a human derived animal model of CC,EC,OC PDX,to identify the biological consistency between the model and the patients' tumor,and to provide a suitable experimental model for the study of new drugs,preclinical trials and individualized treatment of gynecological cancer.Methods: The first generation(P1generation)PDX model was established by subcutaneous transplantation of 15 frozen CC,EC and OC patients from the gynaecological center of the First Affiliated Hospital of Xinjiang Medical University.The weight and tumor volume of tumor bearing mice were monitored The second generation(P2generation)PDX model was established after 3-size tumors were transplanted and passed on after tumorigenesis.The clinical data of the collected clinical specimens were recorded,and the correlation between the tumor rate and the clinical data was statistically analyzed.In addition,the recovery experiment was carried out to detect the activity and tumorigenicity of the patient's cryopreserved tumor.HE staining and immunohistochemical staining were performed on the tumor tissue and its corresponding transplanted tumor.Results: In this study,the success rate of CC,EC,OC PDX model was 53%(8/15),cervical cancer model was 60%(3/5),ovarian cancer model was 40%(2/5),endometrial cancer model was 60%(3/5),P2,P3 tumor formation rate was 100%,and transplanted tumor grew well.Statistical analysis showed that there was no statistical significance between the tumor formation rate and clinical stage(P=0.461),between the tumor formation rate and surgical pathological classification of patients(P=0.6042),and between the time of sample in vitro and the tumor formation rate(P=0.7821).There was a significant difference between tumor formation rate and preoperative neoadjuvant chemotherapy(P=0.0125).The histopathological morphology of the transplanted tumor was consistent with that of the corresponding tissue by HE staining,and the positive rate of the original immunohistochemical staining was consistent with that of the transplanted tumor(p16 and p53).Conclusion: The successful construction of CC,EC,OC PDX models in P1 and P2 generations,the growth of transplanted tumor is good,and it has statistical significance with whether new adjuvant treatment is performed before operation,which provides experimental basis for the follow-up better research and development of CC,EC,OC PDX models.The PDX model in this study can provide an experimental platform for clinical drug screening and individualized treatment of CC,EC and OC.