Volume 118, May 2023, 110030Author links open overlay panel, , , , , , , , Highlights•

IKBIP was identified as an independent prognostic factor for GBM.

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Prognostic model combining the expression of IKBIP with other clinical factors helped to predict the prognosis for GBM patients.

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Differential abundances of immune cells and pathway enrichments analyses helped to understand the potential mechanisms of IKBIP involved in GBM.

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The impact of IKBIP on GBM cell invasion, proliferation, and senescence was observed through in vitro experiment.

AbstractBackground

Due to the negative association between inhibitor of nuclear factor-kB kinase-interacting protein (IKBIP) and survival in gliomas, this study aimed to comprehensively analyze the potential function of IKBIP in glioblastoma multiforme (GBM).

Methods

GBM samples were retrieved from The Cancer Genome Atlas and Chinese Glioma Genome Atlas as training and validation cohorts, respectively, and survival and Cox regression analyses were conducted. Based on clinical indicators and IKBIP, three prognostic models were established and then verified using the validation dataset. Infiltrating immune cell analysis and single-sample gene set enrichment analysis were also conducted to explore the underlying mechanisms. Finally, the key findings were validated through molecular biology experiments.

Results

Patients in the high IKBIP score group had poorer survival. Based on Cox regression and subgroup analyses, IKBIP was identified as an independent prognostic factor. Among the three models constructed, the model combining the IKBIP signature and clinical features displayed good performance in terms of discrimination, calibration, and model improvement capability in the training cohort. This model was also successfully validated in an external cohort from the CGGA. Further analysis revealed that many immune cells and related pathways were involved in the high-risk group. In vitro experiments revealed that the knockdown of IKBIP inhibited cell invasion and proliferation, and promoted their senescence.

Conclusions

The prognostic value of IKBIP and its positive impact on the invasiveness of GBM were identified, indicating that IKBIP may serve as an underlying target for the treatment of GBM.

Keywords

Glioblastoma

IKBIP

Prognosis

STAT3 pathway

EMT

AbbreviationsANOVA

analysis of variance

APAF1

apoptotic protease-activating factor-1

CGGA

Chinese Glioma Genome Atlas

DCA

decision curve analysis

EMT

epithelial-to-mesenchymal transition

GBM

glioblastoma multiforme

GEPIA2

Gene Expression Profiling Interactive Analysis

GSVA

gene set variation analysis

GTEx

Genome Tissues Expression

IDI

integrated discrimination improvement

IKBIP

inhibitor of nuclear factor kappa-B kinase-interacting protein

LOESS

locally estimated scatterplot smoothing

MSigDB

Molecular Signatures Database

NRI

net reclassification improvement

ROC

receiver operating characteristic

RT-qPCR

real-time quantitative polymerase chain reaction

ssGSEA

single sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

UCSC

University of California Santa Cruz

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