Please use this identifier to cite or link to this item: doi:10.22028/D291-41962
Title: Proteomic Analysis of Spatial Heterogeneity Identifies HMGB2 as Putative Biomarker of Tumor Progression in Adult-Type Diffuse Astrocytomas
Author(s): Becker, Aline P.
Becker, Valesio
McElroy, Joseph
Webb, Amy
Han, Chunhua
Guo, Yingshi
Bell, Erica H.
Fleming, Jessica
Popp, Ilinca
Staszewski, Ori
Prinz, Marco
Otero, Jose J.
Haque, Saikh Jaharul
Grosu, Anca-Ligia
Chakravarti, Arnab
Language: English
Title: Cancers
Volume: 16
Issue: 8
Publisher/Platform: MDPI
Year of Publication: 2024
Free key words: tumor heterogeneity
mass spectrometry
proteomic profile
HMGB2
glioma
glioblastoma
gene methylation
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Although grading is defined by the highest histological grade observed in a glioma, most high-grade gliomas retain areas with histology reminiscent of their low-grade counterparts. We sought to achieve the following: (i) identify proteins and molecular pathways involved in glioma evolution; and (ii) validate the high mobility group protein B2 (HMGB2) as a key player in tumor progression and as a prognostic/predictive biomarker for diffuse astrocytomas. We performed liquid chromatography tandem mass spectrometry (LC-MS/MS) in multiple areas of adult-type astrocytomas and validated our finding in multiplatform-omics studies and high-throughput IHC analysis. LC-MS/MSdetected proteomic signatures characterizing glioma evolution towards higher grades associated with, but not completely dependent, on IDH status. Spatial heterogeneity of diffuse astrocytomas was associated with dysregulation of specific molecular pathways, and HMGB2 was identified as a putative driver of tumor progression, and an early marker of worse overall survival in grades 2 and 3 diffuse gliomas, at least in part regulated by DNA methylation. In grade 4 astrocytomas, HMGB2 expression was strongly associated with proliferative activity and microvascular proliferation. Grounded in proteomic findings, our results showed that HMGB2 expression assessed by IHC detected early signs of tumor progression in grades 2 and 3 astrocytomas, as well as identified GBMs that had a better response to the standard chemoradiation with temozolomide.
DOI of the first publication: 10.3390/cancers16081516
URL of the first publication: https://doi.org/10.3390/cancers16081516
Link to this record: urn:nbn:de:bsz:291--ds-419624
hdl:20.500.11880/37554
http://dx.doi.org/10.22028/D291-41962
ISSN: 2072-6694
Date of registration: 29-Apr-2024
Description of the related object: Supplementary Materials
Related object: https://www.mdpi.com/article/10.3390/cancers16081516/s1
Faculty: M - Medizinische Fakultät
Department: M - Neuropathologie
Professorship: M - Prof. Dr. Walter Schulz-Schaeffer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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