Overexpression of key complement regulators in glioblastoma.

Overview

Authors: Linnea Blomberg¹, Leonora Raba¹, Johan Bengzon², Kurt Osther¹, Henrietta Nittby Redebrandt^1,2

ORCID iDs: Henrietta Nittby Redebrandt

Division of Clinical Sciences, Department of Neurosurgery, Rausing Laboratory, Lund University, Lund, Sweden
Department of Neurosurgery, Skåne University Hospital, Lund, Sweden

Institutions: Lund University (Sweden); Skåne University Hospital (Sweden)

Journal: PloS one, volume 21, issue 5, article e0349101

Dates: received 30 September 2025; accepted 24 April 2026; published online 15 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1371/journal.pone.0349101 · PMID 42139305 · PMCID PMC13178988 · OpenAlex W7161258882

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: genetics / omics (modality), human (organism), rat (organism), other condition (population), cellular / molecular (subfield)

Methods: Spectral & time-frequency, Statistics, Evoked potentials

MeSH: Brain Neoplasms*, Complement System Proteins*, Gene Expression Regulation, Neoplastic*, Glioblastoma*, Animals, C-Reactive Protein, Cell Line, Tumor, Complement C1 Inhibitor Protein, Complement Factor H, Gene Expression Profiling, Humans, Nerve Tissue Proteins, Pentraxins, Rats, Serum Amyloid P-Component (* major topic)

Topic: Biomarkers in Disease Mechanisms (Immunology, Immunology and Microbiology), according to OpenAlex

Funding: Cancerfonden (25 4458 Pj, 22 2100 Pj 01 H); Region Skåne (ALF Young Researcher)

Citations: cited by 1 paper (Europe PMC); 71 references in the paper

Abstract

Background: Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor in adults. While immune evasion is a well-recognized driver of GBM progression and a major obstacle for efficient immunotherapy, the role of the complement system remains underexplored. C1-inhibitor (C1-INH), a regulator of complement activation, was recently found overexpressed in GBM. We therefore hypothesized that GBM overexpresses additional complement regulators beyond C1-INH and the present work aimed to identify these.

Method: Gene expression of complement inhibitors, the complement regulator pentraxin-3 (PTX3), and complement proteins was analyzed across nine publicly available transcriptomic datasets. Within each dataset, statistical comparisons were performed between sample groups for each gene. Differentially expressed complement inhibitors were validated at the protein level by immunostaining in the rat GBM cell line NS1 and patient derived GBM tissue.

Results: CFI, encoding factor I, was significantly overexpressed in GBM compared to non-tumoral brain, while THBD and CFH, encoding thrombomodulin and factor H, displayed moderate overexpression. SERPING1, encoding C1-INH, was also upregulated, confirming previous findings. Immunostaining confirmed the expression of these inhibitors in vitro as well as in human glioblastoma tissue. Additionally, PTX3 and early complement proteins were significantly overexpressed in GBM, while levels of C5 and downstream components were comparable to normal brain.

Conclusions: Our findings indicate that the GBM tumor overexpresses a specific set of complement regulators and components of the complement cascade, possibly inhibiting an efficient anti-tumoral immune response. Further investigations of these regulators as potential therapeutical targets in GBM are therefore highly warranted.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

geo:GSE263588 — at NCBI GEO; found in the references

Data Availability

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 15 MeSH terms, 2 funders, 62 references.

Cite

This paper

Blomberg, L., Raba, L., Bengzon, J., Osther, K., & Nittby Redebrandt, H. (2026). Overexpression of key complement regulators in glioblastoma. PloS one, 21(5), e0349101. https://doi.org/10.1371/journal.pone.0349101

BibTeX

@article{blomberg2026overexpression, author = {Blomberg, Linnea and Raba, Leonora and Bengzon, Johan and Osther, Kurt and Nittby Redebrandt, Henrietta}, title = {{Overexpression of key complement regulators in glioblastoma}}, journal = {PloS one}, year = {2026}, month = may, volume = {21}, number = {5}, pages = {e0349101}, publisher = {PLOS}, issn = {1932-6203}, doi = {10.1371/journal.pone.0349101}, url = {https://doi.org/10.1371/journal.pone.0349101}, pmid = {42139305}, pmcid = {PMC13178988} }

RIS

TY - JOUR AU - Blomberg, Linnea AU - Raba, Leonora AU - Bengzon, Johan AU - Osther, Kurt AU - Nittby Redebrandt, Henrietta TI - Overexpression of key complement regulators in glioblastoma T2 - PloS one J2 - PLoS One PY - 2026 DA - 2026/05/15 VL - 21 IS - 5 SP - e0349101 SN - 1932-6203 PB - PLOS DO - 10.1371/journal.pone.0349101 UR - https://doi.org/10.1371/journal.pone.0349101 LA - en ER -

CSL-JSON

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