% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{SalvianoSilva:299581,
      author       = {A. Salviano-Silva and K. Wollmann and S. Brenna and R.
                      Reimer and J. E. Neumann and M. Dottermusch and L. Woythe
                      and C. L. Maire and B. Puig and U. Schüller and M. J. Saul
                      and M. Westphal and R. Drexler and L. Dührsen and J. Gempt
                      and D. H. Heiland$^*$ and K. Lamszus and F. L. Ricklefs},
      title        = {{E}xtracellular {V}esicles {C}arrying {T}enascin-{C} are
                      {C}linical {B}iomarkers and {I}mprove {T}umor-{D}erived
                      {DNA} {A}nalysis in {G}lioblastoma {P}atients.},
      journal      = {ACS nano},
      volume       = {19},
      number       = {10},
      issn         = {1936-0851},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DKFZ-2025-00522},
      pages        = {9844-9859},
      year         = {2025},
      note         = {2025 Mar 18;19(10):9844-9859},
      abstract     = {Extracellular vesicles (EVs) act as carriers of biological
                      information from tumors to the bloodstream, enabling the
                      detection of circulating tumor material and tracking of
                      disease progression. This is particularly crucial in
                      glioblastoma, a highly aggressive and heterogeneous tumor
                      that is challenging to monitor. Using imaging flow cytometry
                      (IFCM), we conducted an immunophenotyping analysis of eight
                      glioma-associated antigens and tetraspanins in plasma EVs
                      from 37 newly diagnosed glioblastoma patients (pre- and
                      post-surgery), 11 matched individuals with recurrent
                      glioblastoma, and 22 healthy donors (HD). Tenascin-C (TNC)
                      positive EVs displayed the strongest differences in newly
                      diagnosed and recurrent glioblastoma patients, when compared
                      to non-tumor subjects. Among dual-positive subpopulations,
                      TNC+/CD9+ EVs were the most elevated in newly diagnosed (FC
                      = 7.6, p <0.0001, AUC = $81\%)$ and recurrent patients (FC =
                      16.5, p <0.0001; AUC = $90\%)$ than HD. In comparison with
                      other CNS tumors (n = 25), this subpopulation was also
                      34.5-fold higher in glioblastoma than in meningioma cases (p
                      <0.01). Additionally, TNC+/CD9+ EV levels were 3.3-fold
                      elevated in cerebrospinal fluid from glioblastoma patients
                      (n = 6) than controls (p <0.05). Aberrant TNC levels were
                      further observed in glioblastoma EVs from different sources
                      and purified via different methods. Immunohistochemical
                      analysis revealed high levels of TNC in tumor tissues.
                      Spatial transcriptomic analysis indicated a TNC
                      overexpression in malignant cell populations of glioblastoma
                      resections, particularly in cells with mesenchymal-like
                      signatures and chromosomal aberrations. Lastly, we purified
                      TNC+ EVs from plasma of 21 glioblastoma patients by magnetic
                      sorting and detected the oncogenic mutation TERT*C228T by
                      droplet digital PCR. The mutant allele frequency was higher
                      in TNC+ EVs vs TNC-negative EVs (FC = 32, p <0.001), total
                      EVs (FC = 5.3, p <0.001) or cell-free DNA (FC = 5.3, p
                      <0.01). In conclusion, circulating TNC+ EVs may have
                      potential as clinical biomarkers in glioblastoma, and their
                      purification could improve the identification of
                      tumor-specific mutations in liquid biopsies.},
      keywords     = {Tenascin-C (Other) / biomarkers (Other) / extracellular
                      vesicles (Other) / glioblastoma (Other) / liquid biopsy
                      (Other)},
      cin          = {FR01},
      ddc          = {540},
      cid          = {I:(DE-He78)FR01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40056466},
      doi          = {10.1021/acsnano.4c13599},
      url          = {https://inrepo02.dkfz.de/record/299581},
}