Integrated analysis of transcriptome in cancer patient-derived xenografts

PLoS One. 2015 May 7;10(5):e0124780. doi: 10.1371/journal.pone.0124780. eCollection 2015.

Abstract

Patient-derived xenograft (PDX) tumor model is a powerful technology in evaluating anti-cancer drugs and facilitating personalized medicines. Multiple research centers and commercial companies have put huge efforts into building PDX mouse models. However, PDX models have not been widely available and their molecular features have not been systematically characterized. In this study, we provided a comprehensive survey of PDX transcriptome by integrating analysis of 58 patients involving 8 different tumors. The median correlation coefficient between patients and xenografts is 0.94, which is higher than that between patients and cell line panel or between patients with the same tumor. Major differential gene expressions in PDX occur in the engraftment of human tumor tissue into mice, while gene expressions are relatively stable over passages. 48 genes are frequently differentially expressed in PDX mice of multiple cancers. They are enriched in extracellular matrix and immune response, and some are reported as targets for anticancer drugs. A simulation study showed that expression change between PDX and patient tumor (6%) would result in acceptable change in drug sensitivity (3%). Our findings demonstrate that PDX mice represent the gene-expression and drug-response features of primary tumors effectively, and it is recommended to monitoring the overall expression profiles and drug target genes in clinical application.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Precision Medicine
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents

Grants and funding

The study was funded by the Shanghai Municipal Commission of Science and Technology (15YF1414100, 14DZ1951300, and 14DZ2252000), Shanghai Institutes for Biological Sciences Knowledge Innovation Program (2014KIP215), and National Basic Scientific Research Fund (2009FY120100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.