Abstract
Cholangiocarcinoma (CCA) is an aggressive cancer with limited effective chemotherapy and targeted therapy options. Existing cell lines and animal models only partially mimic the characteristics of the tumor, highlighting the need for more effective models to study the biology of cancer and drug responses. This study aimed to establish and characterize patient-derived xenograft (PDX) models of CCA. Tumor samples from 40 CCA patients were subcutaneously implanted into non-obese diabetic/ShiJic-severe combined immunodeficiency Jcl mice to establish patient-derived xenograft (PDX) models. Successfully engrafted tumors were passaged across three generations. Histological features were analyzed using H&E staining and immunohistochemistry for cytokeratin-19, cytokeratin-7, heppar-1 and arginase-1. Whole exome sequencing (WES) was performed to assess genetic stability and identify somatic mutations. A total of eight PDX models were successfully created, representing 20% of the total cases. Histological comparisons showed strong concordance between patient tumors and their corresponding xenografts in the eight PDX models across generations. WES analysis confirmed the genetic stability of the PDX models, with significant somatic mutations identified in key genes such as TTN, MUC12, ARID1A, TP53, and RNF43. The CCA PDX model could reflect both the histological and genetic characteristics of the original tumors, providing a valuable tool for studying tumor biology and serving as a preclinical model to develop personalized treatment options for CCA.
Published Version
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