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Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors.

Chandran UR, Dhir R, Ma C, Michalopoulos G, Becich M, Gilbertson J - BMC Cancer (2005)

Bottom Line: Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue.These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA. chandran@pitt.edu <chandran@pitt.edu>

ABSTRACT

Background: Typical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies.

Methods: To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors.

Results: Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.

Conclusions: The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

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Related in: MedlinePlus

Overlayed SAM plots (for details, see Materials and Methods) from the donor v tumor, donor v adjacent normal and tumor v adjacent normal analyses. Each of the SAM plots was overlayed to direct comparison of the plots. The diagonal line represents no differential gene expression where the observed d value equals the expected d value after 1000 permutations of the class labels. Genes that are differentially expressed are displaced from the diagonal (greater than 0 for up regulation and less than 0 for down regulation). Genes that are more differentially expressed are more displaced from the diagonal than those that are closer to the diagonal. For each of the comparisons, a plot is generated from the d values of the 12625 probe sets in the two specimen groups. Red = donor v tumor plot; green = adjacent normal v tumor plot; black = adjacent normal v donor plot.
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Figure 3: Overlayed SAM plots (for details, see Materials and Methods) from the donor v tumor, donor v adjacent normal and tumor v adjacent normal analyses. Each of the SAM plots was overlayed to direct comparison of the plots. The diagonal line represents no differential gene expression where the observed d value equals the expected d value after 1000 permutations of the class labels. Genes that are differentially expressed are displaced from the diagonal (greater than 0 for up regulation and less than 0 for down regulation). Genes that are more differentially expressed are more displaced from the diagonal than those that are closer to the diagonal. For each of the comparisons, a plot is generated from the d values of the 12625 probe sets in the two specimen groups. Red = donor v tumor plot; green = adjacent normal v tumor plot; black = adjacent normal v donor plot.

Mentions: To determine the statistical significance of the observed differential expression between the three specimen groups, SAM analysis was performed. From each comparison (tumor v adjacent normal, tumor v donor and adjacent normal v donor), a SAM plot was generated and the plots for the three comparisons were overlaid (Fig 3). The diagonal line in Figure 3 represents no differential expression (identical observed and expected d values, for further details see Materials and Methods) with points displaced from the diagonal representing differential expression. Figure 3 shows that each of the comparisons yields a distinct expression profile with donor v tumor exhibiting more differential expression than adjacent normal v tumor or donor v adjacent normal.


Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors.

Chandran UR, Dhir R, Ma C, Michalopoulos G, Becich M, Gilbertson J - BMC Cancer (2005)

Overlayed SAM plots (for details, see Materials and Methods) from the donor v tumor, donor v adjacent normal and tumor v adjacent normal analyses. Each of the SAM plots was overlayed to direct comparison of the plots. The diagonal line represents no differential gene expression where the observed d value equals the expected d value after 1000 permutations of the class labels. Genes that are differentially expressed are displaced from the diagonal (greater than 0 for up regulation and less than 0 for down regulation). Genes that are more differentially expressed are more displaced from the diagonal than those that are closer to the diagonal. For each of the comparisons, a plot is generated from the d values of the 12625 probe sets in the two specimen groups. Red = donor v tumor plot; green = adjacent normal v tumor plot; black = adjacent normal v donor plot.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173092&req=5

Figure 3: Overlayed SAM plots (for details, see Materials and Methods) from the donor v tumor, donor v adjacent normal and tumor v adjacent normal analyses. Each of the SAM plots was overlayed to direct comparison of the plots. The diagonal line represents no differential gene expression where the observed d value equals the expected d value after 1000 permutations of the class labels. Genes that are differentially expressed are displaced from the diagonal (greater than 0 for up regulation and less than 0 for down regulation). Genes that are more differentially expressed are more displaced from the diagonal than those that are closer to the diagonal. For each of the comparisons, a plot is generated from the d values of the 12625 probe sets in the two specimen groups. Red = donor v tumor plot; green = adjacent normal v tumor plot; black = adjacent normal v donor plot.
Mentions: To determine the statistical significance of the observed differential expression between the three specimen groups, SAM analysis was performed. From each comparison (tumor v adjacent normal, tumor v donor and adjacent normal v donor), a SAM plot was generated and the plots for the three comparisons were overlaid (Fig 3). The diagonal line in Figure 3 represents no differential expression (identical observed and expected d values, for further details see Materials and Methods) with points displaced from the diagonal representing differential expression. Figure 3 shows that each of the comparisons yields a distinct expression profile with donor v tumor exhibiting more differential expression than adjacent normal v tumor or donor v adjacent normal.

Bottom Line: Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue.These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA. chandran@pitt.edu <chandran@pitt.edu>

ABSTRACT

Background: Typical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies.

Methods: To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors.

Results: Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.

Conclusions: The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

Show MeSH
Related in: MedlinePlus