Format

Send to

Choose Destination
Neuro Oncol. 2018 May 18;20(6):776-787. doi: 10.1093/neuonc/nox234.

An NF-κB signature predicts low-grade glioma prognosis: a precision medicine approach based on patient-derived stem cells.

Author information

1
Department of Neurosurgery, University Hospital of Udine, Udine, Italy.
2
Laboratorio Nazionale, Consorzio Interuniversitario Biotecnologie (LNCIB), Trieste, Italy.
3
Department of Medicine, University of Udine, Udine, Italy.
4
Department of Pathology, University Hospital of Udine, Udine, Italy.
5
IGA Technology Services Srl, Udine, Italy.
6
Bioinformatics Core Facility, Centre for Integrative Biology, CIBIO, University of Trento, Trento, Italy.

Abstract

Background:

While recent genome-wide association studies have suggested novel low-grade glioma (LGG) stratification models based on a molecular classification, we explored the potential clinical utility of patient-derived cells. Specifically, we assayed glioma-associated stem cells (GASC) that are patient-derived and representative of the glioma microenvironment.

Methods:

By next-generation sequencing, we analyzed the transcriptional profile of GASC derived from patients who underwent anaplastic transformation either within 48 months (GASC-BAD) or ≥7 years (GASC-GOOD) after surgery. Gene set enrichment and pathway enrichment analyses were applied. The prognostic role of a nuclear factor-kappaB (NF-κB) signature derived from GASC-BAD was tested in 530 newly diagnosed diffuse LGG patients comprised within The Cancer Genome Atlas (TCGA) database. The prognostic value of the GASC upstream regulator p65 NF-κB was assessed, by univariate and multivariate Cox analyses, in a single center case study, including 146 grade II LGGs.

Results:

The key elements differentiating the transcriptome of GASC isolated from LGG with different prognoses were mostly related to hallmarks of cancer (eg, inflammatory/immune process, NF-κB activation). Consistently, the NF-κB signature extrapolated from the GASC study was prognostic in the dataset of TCGA. Finally, the nuclear expression of the NF-kB-p65 protein, assessed using an inexpensive immunohistochemical method, was an independent predictor of both overall survival and malignant progression-free survival in 146 grade II LGGs.

Conclusion:

This study demonstrates for the first time the independent prognostic role of NF-kB activation in LGG and outlines the role of patient-based stem cell models as a tool for precision medicine approaches.

PMID:
29228370
PMCID:
PMC5961156
DOI:
10.1093/neuonc/nox234
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center