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Glioblastoma pseudoprogression and true progression reveal spatially variable transcriptional differences.

Authors :
Wang, Wesley
Tugaoen, Jonah Domingo
Fadda, Paolo
Toland, Amanda Ewart
Ma, Qin
Elder, J. Brad
Giglio, Pierre
Ong, Shirley
Pillainayagam, Clement
Gornanovich, Justin
Gould, Megan
Lima, Judith
Lonser, Russell
Elder, Brad
Hardesty, Douglas
Lucas, Timothy
Ahmadian, Saman
Kobalka, Peter
Thomas, Diana
Slone, Wayne
Source :
Acta Neuropathologica Communications. 12/4/2023, Vol. 11 Issue 1, p1-18. 18p.
Publication Year :
2023

Abstract

Post-resection radiologic monitoring to identify areas of new or progressive enhancement concerning for cancer recurrence is critical during patients with glioblastoma follow-up. However, treatment-related pseudoprogression presents with similar imaging features but requires different clinical management. While pathologic diagnosis is the gold standard to differentiate true progression and pseudoprogression, the lack of objective clinical standards and admixed histologic presentation creates the needs to (1) validate the accuracy of current approaches and (2) characterize differences between these entities to objectively differentiate true disease. We demonstrated using an online RNAseq repository of recurrent glioblastoma samples that cancer-immune cell activity levels correlate with heterogenous clinical outcomes in patients. Furthermore, nCounter RNA expression analysis of 48 clinical samples taken from second neurosurgical resection supports that pseudoprogression gene expression pathways are dominated with immune activation, whereas progression is predominated with cell cycle activity. Automated image processing and spatial expression analysis however highlight a failure to apply these broad expressional differences in a subset of cases with clinically challenging admixed histology. Encouragingly, applying unsupervised clustering approaches over our segmented histologic images provides novel understanding of morphologically derived differences between progression and pseudoprogression. Spatially derived data further highlighted polarization of myeloid populations that may underscore the tumorgenicity of novel lesions. These findings not only help provide further clarity of potential targets for pathologists to better assist stratification of progression and pseudoprogression, but also highlight the evolution of tumor-immune microenvironment changes which promote tumor recurrence. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20515960
Volume :
11
Issue :
1
Database :
Academic Search Index
Journal :
Acta Neuropathologica Communications
Publication Type :
Academic Journal
Accession number :
173994082
Full Text :
https://doi.org/10.1186/s40478-023-01587-w