Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization.

Abstract

Simple SummaryThe rate of total tumor engraftment of patient-derived xenografts is 50% in cervical cancer. These cancers retain their histopathological characteristics. The gene mutations and expression patterns associated with carcinogenesis and infiltration and the expression levels of genes in extracellular vesicles released from the tumors are similar between patient-derived xenograft models and primary tumors. Patient-derived xenograft models of cervical cancer could be potentially useful tools for translational research.Patient-derived xenograft (PDX) models are useful tools for preclinical drug evaluation, biomarker identification, and personalized medicine strategies, and can be developed by the heterotopic or orthotopic grafting of surgically resected tumors into immunodeficient mice. We report the PDX models of cervical cancer and demonstrate the similarities among original and different generations of PDX tumors. Fresh tumor tissues collected from 22 patients with primary cervical cancer were engrafted subcutaneously into NOD.CB17-PrkdcSCID/J mice. Histological and immunohistochemical analyses were performed to compare primary and different generations of PDX tumors. DNA and RNA sequencing were performed to verify the similarity between the genetic profiles of primary and PDX tumors. Total RNA in extracellular vesicles (EVs) released from primary and PDX tumors was also quantified to evaluate gene expression. The total tumor engraftment rate was 50%. Histologically, no major differences were observed between the original and PDX tumors. Most of the gene mutations and expression patterns related to carcinogenesis and infiltration were similar between the primary tumor and xenograft. Most genes associated with carcinogenesis and infiltration showed similar expression levels in the primary tumor and xenograft EVs. Therefore, compared with primary tumors, PDX models could be potentially more useful for translational research.