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 |
Files for this record:
File | Description | Size | Format | |
---|---|---|---|---|
cancers-16-01516-v2.pdf | 3,38 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License