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Orth, Martin F.; Gerke, Julia S.; Knösel, Thomas; Altendorf‐Hofmann, Annelore; Musa, Julian; Alba‐Rubio, Rebeca; Stein, Stefanie; Hölting, Tilman L. B.; Cidre‐Aranaz, Florencia; Romero‐Pérez, Laura; Dallmayer, Marlene; Baldauf, Michaela C.; Marchetto, Aruna; Sannino, Giuseppina; Knott, Maximilian M. L.; Wehweck, Fabienne; Ohmura, Shunya; Li, Jing; Hakozaki, Michiyuki; Kirchner, Thomas; Dandekar, Thomas; Butt, Elke; Grünewald, Thomas G. P.

Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma

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  • Medientyp: E-Artikel
  • Titel: Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma
  • Beteiligte: Orth, Martin F.; Gerke, Julia S.; Knösel, Thomas; Altendorf‐Hofmann, Annelore; Musa, Julian; Alba‐Rubio, Rebeca; Stein, Stefanie; Hölting, Tilman L. B.; Cidre‐Aranaz, Florencia; Romero‐Pérez, Laura; Dallmayer, Marlene; Baldauf, Michaela C.; Marchetto, Aruna; Sannino, Giuseppina; Knott, Maximilian M. L.; Wehweck, Fabienne; Ohmura, Shunya; Li, Jing; Hakozaki, Michiyuki; Kirchner, Thomas; Dandekar, Thomas; Butt, Elke; Grünewald, Thomas G. P.
  • Erschienen: Wiley, 2019
  • Erschienen in: International Journal of Cancer
  • Sprache: Englisch
  • DOI: 10.1002/ijc.31903
  • ISSN: 0020-7136; 1097-0215
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:label /><jats:p>Soft‐tissue sarcomas are rare, heterogeneous, and often aggressive mesenchymal cancers. Many of them are associated with poor outcome, partially because biomarkers that can identify high‐risk patients are lacking. Studies on sarcomas are often limited by small sample‐sizes rendering the identification of biomarkers difficult when focusing on individual cohorts. However, the increasing number of publicly available ‘omics’ data opens inroads to overcome this obstacle.</jats:p><jats:p>Here, we combine transcriptome analyses, immunohistochemistry, and functional assays to show that high adenosine monophosphate deaminase 2 (AMPD2) is a robust prognostic biomarker for worse outcome in undifferentiated pleomorphic sarcoma (UPS).</jats:p><jats:p>Gene expression and survival data for UPS from two independent studies were subjected to survival association‐testing. Genes, whose high expression was significantly correlated with worse outcome in both cohorts, were considered as biomarker candidates. The best candidate, <jats:italic>AMPD2</jats:italic>, was validated in a tissue microarray. Analysis of DNA copy‐number data and matched transcriptomes indicated that high <jats:italic>AMPD2</jats:italic> expression is significantly correlated with gains at the <jats:italic>AMPD2</jats:italic> locus. Gene set enrichment analyses of <jats:italic>AMPD2</jats:italic> co‐expressed genes in both transcriptome datasets suggested that <jats:italic>AMPD2</jats:italic>‐high UPS are enriched in tumorigenic signatures. Consistently, knockdown of <jats:italic>AMPD2</jats:italic> by RNA interference in an UPS cell line inhibited proliferation <jats:italic>in vitro</jats:italic> and tumorigenicity <jats:italic>in vivo</jats:italic>.</jats:p><jats:p>Collectively, we provide evidence that <jats:italic>AMPD2</jats:italic> may serve as a biomarker for outcome prediction in UPS. Our study exemplifies how the integration of ‘omics’ data, immunohistochemistry, and functional experiments can identify novel biomarkers even in a rare sarcoma, which may serve as a blueprint for biomarker identification for other rare cancers.</jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang