Patient-derived orthotopic xenograft glioma models fail to replicate the magnetic resonance imaging features of the original patient tumor

Patient-derived orthotopic glioma xenograft models are important platforms used for pre-clinical research of glioma. In the present study, the diagnostic ability of magnetic resonance imaging (MRI) was examined with regard to the identification of biomarkers obtained from patient-derived glioma xenografts and human tumors. Conventional MRI, diffusion weighted imaging and dynamic contrast-enhanced (DCE)-MRI were used to analyze seven pairs of high grade gliomas with their corresponding xenografts obtained from non-obese diabetic-severe-combined immunodeficiency nude mice. Tumor samples were collected for transcriptome sequencing and histopathological staining, and differentially expressed genes were screened between the original tumors and the corresponding xenografts. Gene Ontology (GO) analysis was performed to predict the functions of these genes. In 6 cases of xenografts with diffuse growth, the degree of enhancement was significantly lower compared with the original tumors. Histopathological staining indicated that the microvascular area and microvascular diameter of the xenografts were significantly lower compared with the original tumors (P=0.009 and P=0.007, respectively). In one case, there was evidence of nodular tumor growth in the mouse. Both MRI and histopathological staining showed a clear demarcation between the transplanted tumors and the normal brain tissues. The relative apparent diffusion coefficient values of the 7 cases examined were significantly higher compared with the corresponding original tumors (P=0.001) and transfer coefficient values derived from DCE-MRI of the tumor area was significantly lower compared with the original tumors (P=0.016). GO analysis indicated that the expression levels of extracellular matrix-associated genes, angiogenesis-associated genes and immune function-associated genes in the original tumors were higher compared with the corresponding xenografts. In conclusion, the data demonstrated that the MRI features of patient-derived xenograft glioma models in mice were different compared with those of the original patient tumors. Differential gene expression may underlie the differences noted in the MRI features between original tumors and corresponding xenografts. The results of the present study highlight the precautions that should be taken when extrapolating data from patient-derived xenograft studies, and their applicability to humans.