Establishment and Clinical Significance of the Patient-Derived Xenograft Model of Colorectal Cancer

建立患者来源的结直肠癌异种移植模型及其临床意义

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Abstract

OBJECTIVES: Patient-derived xenograft (PDX) models are widely acknowledged for their ability to reflect the heterogeneity of human cancers and can be used to improve preclinical models. In this study, we evaluated the factors affecting the tumor formation rate of the PDX colorectal cancer (CRC) model and conducted preliminary drug sensitivity tests. METHODS: CRC patients who underwent elective surgery at Shaoxing People's Hospital from November 2019 to October 2020 were included. The tumor tissue obtained from surgery was transplanted to the back of NSG mice, and the PDX model was established and subcultured to the F3 generation. Factors that affected tumorigenicity were analyzed and compared histologically. Drug interventions included 5-fluorouracil, oxaliplatin, and propofol. RESULTS: Sixty CRC patients were included in this study, and tumorigenesis was observed in CRC tissue derived from 37 cases (62%). The primary tumor malignancy degree (tumor stage and degree of cell differentiation), preoperative carcinoembryonic antigen level, and tumor location in CRC patients could affect the tumorigenicity of the PDX model. Histopathological analysis of CRC-PDX transplanted tumor tissue was highly consistent with the patient's tumor tissue. All four chemotherapy regimens could inhibit tumor growth and cause tumor tissue damage. Propofol could inhibit diarrhea in mice and protect intestinal mucosa. CONCLUSIONS: The CRC-PDX model established in this study can maintain the biological characteristics of primary tumors and can be used as a reference model for the individualized treatment of CRC patients. The degree of malignancy of the primary tumor is the primary factor affecting the tumorigenesis rate of the PDX model.

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