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Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor models.

Yang X, Lee Y, Huang Y, Chen JL, Xing RH, Lussier YA - BMC Bioinformatics (2010)

Bottom Line: We hypothesized that we could exploit the interspecies genetic differences in these experiments.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu

ABSTRACT

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.

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Related in: MedlinePlus

A simulated visual model of differential genes expression in a xenograft experiment. The numbers in the plot are the simulated gene symbols of differentially expressed probes. Legend: a, b: two sample groups; c: effect of interested; i: probe id; FC: fold change (Equation. 1).
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Figure 2: A simulated visual model of differential genes expression in a xenograft experiment. The numbers in the plot are the simulated gene symbols of differentially expressed probes. Legend: a, b: two sample groups; c: effect of interested; i: probe id; FC: fold change (Equation. 1).

Mentions: We make standard stochastic assumptions about the errors ε, ε’ and ε”. As shown in Figure 2, when Xhyb human probes are exposed to both human and mouse RNA, their major expression levels reflect the expression of their homologous mouse genes. Thus, the GO terms enriched in these cross-species hybridizing human gene targets represent the stromal response of their homologous mouse genes. In contrast, in the remaining deregulated genes (remaining genes) that are putatively enriched in cancer cell signal, the majority of gene expressions were contributed by designed targets which reflect the tumor biological processes of human tumor tissues.


Stromal microenvironment processes unveiled by biological component analysis of gene expression in xenograft tumor models.

Yang X, Lee Y, Huang Y, Chen JL, Xing RH, Lussier YA - BMC Bioinformatics (2010)

A simulated visual model of differential genes expression in a xenograft experiment. The numbers in the plot are the simulated gene symbols of differentially expressed probes. Legend: a, b: two sample groups; c: effect of interested; i: probe id; FC: fold change (Equation. 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967741&req=5

Figure 2: A simulated visual model of differential genes expression in a xenograft experiment. The numbers in the plot are the simulated gene symbols of differentially expressed probes. Legend: a, b: two sample groups; c: effect of interested; i: probe id; FC: fold change (Equation. 1).
Mentions: We make standard stochastic assumptions about the errors ε, ε’ and ε”. As shown in Figure 2, when Xhyb human probes are exposed to both human and mouse RNA, their major expression levels reflect the expression of their homologous mouse genes. Thus, the GO terms enriched in these cross-species hybridizing human gene targets represent the stromal response of their homologous mouse genes. In contrast, in the remaining deregulated genes (remaining genes) that are putatively enriched in cancer cell signal, the majority of gene expressions were contributed by designed targets which reflect the tumor biological processes of human tumor tissues.

Bottom Line: We hypothesized that we could exploit the interspecies genetic differences in these experiments.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Genetic Medicine, Dept, of Medicine, University of Chicago, IL, USA. xyang2@uchicago.edu

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus