Establishment of a PDX tumor from Hepatitis C Associated Liver Cancer and Evaluation of Imatinib Treatment Efficacy.

: Chronic hepatitis C virus (HCV) infection is one of the major etiological factors for hepatocellular carcinoma (HCC). The treatment options for HCC are limited for lack of a convenient animal model for study with HCV infection and liver pathogenesis. We aimed at developing a patient-derived xenograft (PDX) tumor in mouse from HCV associated HCC patient and evaluated therapeutic potential. After resection of the primary tumor from patient liver, excess viable tumor was implanted into highly immunodeficient mice. A mouse xenograft tumor line was developed and the tumor was successfully passaged for at least three rounds in immunodeficient mice. The patient's primary tumor and the mouse xenografts were histologically similar. Genetic profiling by short tandem repeat analysis verified that the HCC-PDX model was derived from the HCC clinical specimen. HCV RNA present in the patient liver specimen was undetectable after passage as xenograft tumors in mouse. Human albumin, α-1-antitrypsin, glypican 3, α-SMA, and collagen type 1A2 markers were detected in human original tumor tissues and xenograft tumors. Both the patient primary tumor and the xenograft tumors had a significantly higher level of c-Kit mRNA. Treatment of HCC-PDX xenograft tumor bearing mice with c-Kit inhibitor, imatinib, significantly reduced tumor growth, and phospho-Akt and cyclin D1 expression, as compared to untreated control tumors. Conclusion: Our results demonstrated an establishment of HCV associated HCC PDX model as a powerful tool for evaluating candidate drugs. Information on molecular changes in cancer associated specific gene expression will facilitate for efficient targeted therapy and treatment strategy.