Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor
Xinan Yang1, Younghee Lee, Yong Huang
1Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu
Background:
Mouse xenograft models, in which human cancer cells are implanted in immune-suppressed mice, have been popular for studying the mechanisms of novel therapeutic targets, tumor progression and metastasis. We hypothesized that we could exploit the interspecies genetic differences in these experiments. Our purpose is to elucidate stromal microenvironment signals from probes on human arrays unintentionally cross-hybridizing with mouse homologous genes in xenograft tumor models.
Results:
By identifying cross-species hybridizing probes from sequence alignment and cross-species hybridization experiment for the human whole-genome arrays, deregulated stromal genes can be identified and then their biological significance were predicted from enrichment studies. Comparing these results with those found by the laser capture microdissection of stromal cells from tumor specimens resulted in the discovery of significantly enriched stromal biological processes.
Conclusions:
Using this method, in addition to their primary endpoints, researchers can leverage xenograft experiments to better characterize the tumor microenvironment without additional costs. The Xhyb probes and R script are available at http://www.lussierlab.org/publications/Stroma.
Insights
Researchers can now analyze mouse xenograft models to understand the tumor microenvironment by identifying cross-species gene expression differences. This method reveals stromal signals without extra costs, aiding cancer research.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Mouse xenograft models are widely used to study cancer progression and therapeutic targets.
- These models involve implanting human cancer cells into immune-suppressed mice.
- Interspecies genetic differences in xenografts present an underexplored opportunity for research.
Purpose of the Study:
- To identify stromal microenvironment signals within xenograft models.
- To leverage unintended cross-hybridization of human array probes with mouse homologous genes.
- To elucidate the biological significance of these cross-species interactions.
Main Methods:
- Identified cross-species hybridizing probes using sequence alignment.
- Performed cross-species hybridization experiments with human whole-genome arrays.
- Predicted biological significance of deregulated stromal genes via enrichment studies.
- Compared findings with laser capture microdissection of stromal cells from human tumor specimens.
Main Results:
- Discovered deregulated stromal genes through cross-species probe analysis.
- Identified significantly enriched stromal biological processes by comparing xenograft data with clinical tumor data.
- Validated the utility of cross-hybridizing probes for microenvironment analysis.
Conclusions:
- A novel method allows researchers to characterize the tumor microenvironment in xenograft models.
- This approach exploits interspecies genetic differences, providing additional insights without increased costs.
- The Xhyb probes and R script are publicly available for broader research application.
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