Regional profiling reveals a distinct glioblastoma infiltrative margin proteome

TL;DR

This study explores the protein differences in different regions of glioblastoma tumors, identifying potential markers for the invasive tumor margin.

Contribution

The paper introduces a novel method to profile the proteome of distinct glioblastoma regions, revealing potential protein markers for the infiltrative margin.

Findings

The proteome of glioblastoma is broadly similar to non-diseased brain tissue.

Cytoplasmic proteins like α-trypsin, actin, apolipoprotein A1, and transthyretin are potentially linked to the tumor's invasive margin.

Methodological approaches were validated for analyzing protein signaling in different tumor regions.

Abstract

Isocitrate dehydrogenase wild-type glioblastoma, a malignant brain tumour of glial origin, confers a poor prognosis with a median survival of 12 to 16 months from diagnosis. Glioblastomas are aggressive tumours that rapidly proliferate and diffusely infiltrate surrounding brain tissue. Current multimodal standard treatment is typically ineffective and despite gross total surgical resection, tumours recur with more aggressive sub-clonal populations of malignant cells. A defining characteristic of glioblastoma is its highly heterogeneous nature and acquirement of somatic mutations advantageous to tumour growth and suppression of apoptotic pathways. Pathogenesis of malignant brain tumours as well as its mode of transformation to a more aggressive subtype is still largely unknown. Although genomic studies have elucidated a plethora of genetic markers associated with glioblastoma subtypes, only a few have been utilised in a clinical setting. One of the emerging approaches to studying glioblastomas is by investigating how an active proteome contributes to its aggressive nature. Furthermore, through activation of specific pathways via post-translational modifications of proteins such as phosphorylation, glioblastomas create an intricate network of signalling pathways which favour tumour growth and proliferation. Here, we investigated the feasibility of diverse methodological approaches to describe abnormal protein signalling across distinct intra-tumour regions of primary glioblastoma tissue, including proliferative core, peripheral rim, and invasive margin. Whilst we observe a broadly comparable proteome relative to the human non-diseased brain, we identify cytoplasmic proteins α-trypsin, actin, apolipoprotein A1 and transthyretin which may putatively be associated with the GBM infiltrative tumour margin.

The online version contains supplementary material available at 10.1038/s41598-025-09228-z.

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