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January 13, 2025
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Multi-omics profiling reveals key factors involved in Ewing sarcoma metastasis.

Publicated to: Molecular Oncology. - 2025-01-05 (), DOI: 10.1002/1878-0261.13788

Authors: Chicón-Bosch M; Sánchez-Serra S; Rosàs-Lapeña M; Costa-Fraga N; Besalú-Velázquez J; Illa-Bernadí J; Mateo-Lozano S; Cidre-Aranaz F; Grünewald TGP; Díaz-Lagares Á; Lopez-Alemany R; Tirado ÒM

Affiliations

Developmental Tumor Biology Laboratory, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain. - Author
Division of Translational Paediatric Sarcoma Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. - Author
Epigenomics Unit, Cancer Epigenomics, Translational Medical Oncology (ONCOMET), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. - Author
Sarcoma Research Group, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Oncobell, L'Hospitalet de Llobregat, Barcelona, Spain. - Author
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Abstract

Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach. Combining transcriptomics, proteomics, and methylomics analyses, we identified signaling cascades and candidate genes enriched in metastases that could be modulating aggressiveness in EWS. Phenotypical validation of two of these candidates, cyclic AMP-responsive element-binding protein 1 (CREB1) and lipoxygenase homology domain-containing protein 1 (LOXHD1), showed an association with migration and clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4) as a CREB1 target interconnecting the different EWS biological layers (RNA, protein and methylation status) and whose high expression is associated with worse clinical outcome. Further studies will provide insight into EWS metastasis mechanisms and ultimately improve survival rates for EWS patients.

Keywords

Creb1Ewing sarcomaFgd4Loxhd1MetastasisMethylomicsMouse modelMulti‐omicsProteomicsTranscriptomics

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Oncology due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous). Notably, the journal is positioned above the 90th percentile.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-13:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 7.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 6 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 12.
  • The number of mentions on the social network X (formerly Twitter): 8 (Altmetric).

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Germany.