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Journal Article Epublish 4 citations

PubMed: 36497479 DOI: 10.3390/cancers14235999

Correlation of Transcriptomics and FDG-PET SUVmax Indicates Reciprocal Expression of Stemness-Related Transcription Factor and Neuropeptide Signaling Pathways in Glucose Metabolism of Ewing Sarcoma.

Cancers (Basel) 14(23)

Authors: Carolin Prexler, Marie Sophie Knape, Janina Erlewein-Schweizer, Wolfgang Roll, Katja Specht, Klaus Woertler, Wilko Weichert, Irene von Luettichau, Claudia Rossig, Julia Hauer, Guenther H S Richter, Wolfgang Weber, Stefan Burdach

Affiliations

  • Department of Pediatrics and Children's Cancer Research Center, Kinderklinik München Schwabing, Klinikum Rechts der Isar, Fakultät für Medizin, Technische Universität München, 80804 Munich, Germany.
  • Institute of Pathology, Technische Universität München, 81675 Munich, Germany.
  • Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Munster, Germany.
  • Musculoskeletal Radiology Section, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
  • German Cancer Consortium (DKTK), Partner Site Munich, 81675 Munich, Germany.
  • ERN PaedCan, 1090 Vienna, Austria.
  • Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, 48149 Muenster, Germany.
  • Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Muenster, 48149 Muenster, Germany.
  • Department of Pediatrics, Division of Oncology and Hematology, Charite-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
  • German Cancer Consortium (DKTK), Partner Site Berlin, 13353 Berlin, Germany.
  • Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, 81675 Munich, Germany.
  • Academy of Translational Medicine and Department of Molecular Oncology-British Columbia Cancer Research Centre, University of British Columbia, 675 West 10th Avenue, Vancouver, BC V5Z 1L3, Canada.

Abstract

BACKGROUND

In Ewing sarcoma (EwS), long-term treatment effects and poor survival rates for relapsed or metastatic cases require individualization of therapy and the discovery of new treatment methods. Tumor glucose metabolic activity varies significantly between patients, and FDG-PET signals have been proposed as prognostic factors. However, the biological basis for the generally elevated but variable glucose metabolism in EwS is not well understood.

METHODS

We retrospectively included 19 EwS samples (17 patients). Affymetrix gene expression was correlated with maximal standardized uptake value (SUVmax) using machine learning, linear regression modelling, and gene set enrichment analyses for functional annotation.

RESULTS

Expression of five genes correlated (, , ) or anticorrelated (, ) significantly with SUVmax (adjusted -value ≤ 0.05). Additionally, we identified 23 genes with large SUVmax effect size, which were significantly enriched for "neuropeptide Y receptor activity (GO:0004983)" (adjusted -value = 0.0007). The expression of the members of this signaling pathway (, , ) anticorrelated with SUVmax. In contrast, three transcription factors associated with maintaining stemness displayed enrichment of their target genes with higher SUVmax: , E2F family, and .

CONCLUSION

Our large-scale analysis examined comprehensively the correlations between transcriptomics and tumor glucose utilization. Based on our findings, we hypothesize that stemness may be associated with increased glucose uptake, whereas neuroectodermal differentiation may anticorrelate with glucose uptake.

MeSH

Genes, Sarcoma, Ewing, Transcription Factors, Neuropeptides, Therapeutics

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