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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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Gene Ontology annotation of differentially expressed gene lists. The fifty most upregulated genes from the donor v tumor, adjacent normal v tumor and tumor v adjacent normal comparisons were uploaded to Affymetrix's Gene Ontology Mining Tool, a, donor v tumor; b, donor v adjacent normal; c adjacent normal v tumor; The annotations is presented as a hierarchy of terms, from general to most specific terms (from left to right). The numbers in parenthesis indicate the number of genes that are annotated with the term. In all of the analysis, annotation of all the submitted probe sets is not achieved. Typically, annotation exists for approximately 60% of the probe sets.
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Figure 4: Gene Ontology annotation of differentially expressed gene lists. The fifty most upregulated genes from the donor v tumor, adjacent normal v tumor and tumor v adjacent normal comparisons were uploaded to Affymetrix's Gene Ontology Mining Tool, a, donor v tumor; b, donor v adjacent normal; c adjacent normal v tumor; The annotations is presented as a hierarchy of terms, from general to most specific terms (from left to right). The numbers in parenthesis indicate the number of genes that are annotated with the term. In all of the analysis, annotation of all the submitted probe sets is not achieved. Typically, annotation exists for approximately 60% of the probe sets.

Mentions: The biological processes regulated in tumors and adjacent normals were also studied using Affymetrix's Gene Ontology Mining tool. The up regulated gene lists obtained at a SAM delta of 2.0 (Table 1) were uploaded to the tool and the resulting annotations examined. Comparison of tumor gene expression to donor expression reveals up-regulation of genes involved in a number of biological processes (Figure 4a). Amongst these are genes involved in apoptosis, cell cycle, cell proliferation, immune response, protein phosphorylation, protein biosynthesis and transcription. A subset of these including genes involved in immune response and transcription are also up-regulated in adjacent normals (Figure 4b). In contrast when tumor expression is compared to adjacent normals, up-regulation of majority of these processes, except protein metabolism, is not detected (Figure 4c).


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)

Gene Ontology annotation of differentially expressed gene lists. The fifty most upregulated genes from the donor v tumor, adjacent normal v tumor and tumor v adjacent normal comparisons were uploaded to Affymetrix's Gene Ontology Mining Tool, a, donor v tumor; b, donor v adjacent normal; c adjacent normal v tumor; The annotations is presented as a hierarchy of terms, from general to most specific terms (from left to right). The numbers in parenthesis indicate the number of genes that are annotated with the term. In all of the analysis, annotation of all the submitted probe sets is not achieved. Typically, annotation exists for approximately 60% of the probe sets.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Gene Ontology annotation of differentially expressed gene lists. The fifty most upregulated genes from the donor v tumor, adjacent normal v tumor and tumor v adjacent normal comparisons were uploaded to Affymetrix's Gene Ontology Mining Tool, a, donor v tumor; b, donor v adjacent normal; c adjacent normal v tumor; The annotations is presented as a hierarchy of terms, from general to most specific terms (from left to right). The numbers in parenthesis indicate the number of genes that are annotated with the term. In all of the analysis, annotation of all the submitted probe sets is not achieved. Typically, annotation exists for approximately 60% of the probe sets.
Mentions: The biological processes regulated in tumors and adjacent normals were also studied using Affymetrix's Gene Ontology Mining tool. The up regulated gene lists obtained at a SAM delta of 2.0 (Table 1) were uploaded to the tool and the resulting annotations examined. Comparison of tumor gene expression to donor expression reveals up-regulation of genes involved in a number of biological processes (Figure 4a). Amongst these are genes involved in apoptosis, cell cycle, cell proliferation, immune response, protein phosphorylation, protein biosynthesis and transcription. A subset of these including genes involved in immune response and transcription are also up-regulated in adjacent normals (Figure 4b). In contrast when tumor expression is compared to adjacent normals, up-regulation of majority of these processes, except protein metabolism, is not detected (Figure 4c).

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