{"title":"Characterization of Patient-derived Xenograft Models of Liver Fluke-associated Cholangiocarcinoma: From Establishment to Molecular Profiling.","authors":"Hasaya Dokduang, Apiwat Jarernrat, Attapol Titapun, Sirinya Sitthirak, Sureerat Padthaisong, Yingpinyapt Kittirat, Sakkarn Sangkamanon, Prakasit Sa-Ngiamwibool, Arporn Wangwiwatsin, Poramate Klanrit, Nisana Namwat, Apinya Jusakul, Yoshinori Murakami, Watcharin Loilome","doi":"10.21873/anticanres.17445","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/aim: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 2","pages":"579-592"},"PeriodicalIF":1.6000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anticancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21873/anticanres.17445","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
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Abstract
Background/aim: 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.
Materials and methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed.
ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies).
Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.
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