9 research outputs found
Proteomic Analysis of Spatial Heterogeneity Identifies HMGB2 as Putative Biomarker of Tumor Progression in Adult-Type Diffuse Astrocytomas
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