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Linking the ovarian cancer transcriptome and immunome.

Rapberger R, Perco P, Sax C, Pangerl T, Siehs C, Pils D, Bernthaler A, Lukas A, Mayer B, Krainer M - BMC Syst Biol (2008)

Bottom Line: Why certain tumor-associated proteins induce an immune response remains largely elusive.Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks.However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, A-1090 Vienna, Austria. ronald.rapberger@univie.ac.at

ABSTRACT

Background: Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive.

Results: This paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients.Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.

Conclusion: A link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.

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Related in: MedlinePlus

Protein networks based on protein-protein interaction data in OPHID. A: Individual interaction networks of Meta-UP, Meta-DOWN, Meta-ALL and SEREX-ovarian datasets as visualized using ProteoLens . B: The indices of aggregation (IA) for the given datasets with respect to the IA of ensembles of randomly generated datasets used as references are shown (means and standard deviations).
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Figure 1: Protein networks based on protein-protein interaction data in OPHID. A: Individual interaction networks of Meta-UP, Meta-DOWN, Meta-ALL and SEREX-ovarian datasets as visualized using ProteoLens . B: The indices of aggregation (IA) for the given datasets with respect to the IA of ensembles of randomly generated datasets used as references are shown (means and standard deviations).

Mentions: We expanded the lists of genes encoded by the datasets using nearest neighbor expansion based on OPHID protein-protein interaction data [42]. This approach is based on the rationale that proteins showing differential abundance might show interactions with other proteins embedded in the same functional context (i.e., their nearest neighbors). The resulting interaction networks, as well as their aggregation indices [27] with respect to a reference curve based on random gene selections, are shown in Figure 1.


Linking the ovarian cancer transcriptome and immunome.

Rapberger R, Perco P, Sax C, Pangerl T, Siehs C, Pils D, Bernthaler A, Lukas A, Mayer B, Krainer M - BMC Syst Biol (2008)

Protein networks based on protein-protein interaction data in OPHID. A: Individual interaction networks of Meta-UP, Meta-DOWN, Meta-ALL and SEREX-ovarian datasets as visualized using ProteoLens . B: The indices of aggregation (IA) for the given datasets with respect to the IA of ensembles of randomly generated datasets used as references are shown (means and standard deviations).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2265674&req=5

Figure 1: Protein networks based on protein-protein interaction data in OPHID. A: Individual interaction networks of Meta-UP, Meta-DOWN, Meta-ALL and SEREX-ovarian datasets as visualized using ProteoLens . B: The indices of aggregation (IA) for the given datasets with respect to the IA of ensembles of randomly generated datasets used as references are shown (means and standard deviations).
Mentions: We expanded the lists of genes encoded by the datasets using nearest neighbor expansion based on OPHID protein-protein interaction data [42]. This approach is based on the rationale that proteins showing differential abundance might show interactions with other proteins embedded in the same functional context (i.e., their nearest neighbors). The resulting interaction networks, as well as their aggregation indices [27] with respect to a reference curve based on random gene selections, are shown in Figure 1.

Bottom Line: Why certain tumor-associated proteins induce an immune response remains largely elusive.Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks.However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Theoretical Chemistry, University of Vienna, Währinger Strasse 17, A-1090 Vienna, Austria. ronald.rapberger@univie.ac.at

ABSTRACT

Background: Autoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive.

Results: This paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients.Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.

Conclusion: A link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.

Show MeSH
Related in: MedlinePlus