A Spatial Molecular Analysis of The Sarcomatous Component in Gliosarcomas

Hüseyinoğlu Z., İnan M. A., Toprak U., Pir M. S., Bilgüvar K., Baykal A. T., ...Daha Fazla

25th American Association of Neurological Surgeons Annual Scientific Meeting, Massachusetts, Amerika Birleşik Devletleri, 25 - 28 Nisan 2025, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Massachusetts
  • Basıldığı Ülke: Amerika Birleşik Devletleri
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

Introduction:

Gliosarcoma is a rare, established histologic subtype of glioblastoma, with malignantglial and

mesenchymal components. Various hypotheses exist regarding its development, one of which

proposes that the sarcomatous component arises from glial cells through epithelial-to-

mesenchymal transition (EMT). To better understand gliosarcoma development and the role

of EMT, we examined spatial molecular alterations across the distinct histological

components of this biphasic tumor.

Methods:

Spatial transcriptomic analysis (Visium, 10x Genomics) was performed in 4 pathologically

confirmed gliosarcoma samples and analyzed for regional variability. Results were validated

using liquid chromatography-mass spectrometry (LC-MS-MS) based proteomic comparison

of the glial and sarcomatous components. Copy number analysis for chromosomes 7 and 10 as

well as TERT mutation was performed using ddPCR and mini-sequencing. Immuno-

histochemistry for chromatin markers, glial and mesenchymal markers, EMT markers as well

as subtyping of immune cells was used to support findings.

Results:

Significant differences in gene expression between the glial and mesenchymal components

were observed in both spatial transcriptomic and proteomic analyses. The tumor

microenvironment was enriched with tumor-associated macrophages (TAMs), confirmed by

immunohistochemistry and spatial analysis. EMT transcription factors were present in each

tumor sample. The mesenchymal component which was particularly abundant around blood

expressed glial stem cell markers. An enrichment analysis indicated to an average of 59

upregulated and 66 downregulated gene-ontology (GO) pathways in the sarcomatous

component.

Conclusion:

Current findings suggest a shared origin of the glial and sarcomatous components in

gliosarcoma and provide insights into the molecular basis of mesenchymal differentiation in

this tumor subtype.