IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma

Abstract

Purpose I kappa B-interacting protein (IKBIP) in cancer has rarely been reported.This study aimed at investigating its expression pattern and biological function in brain glioma at transcriptional level. MethodsWe selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. ResultsWe found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in IDH wildtype and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent GSEA analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed GSVA analysis to screen the EMT-related signaling pathways, and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-β pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1.Finally, higher IKBIP indicated significantly shorter survival for glioma patients.Conclusions IKBIP was associated with more aggressive phenotypes of gliomas. 3 Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.

Disrupting the CmP signaling network unveils novel biomarkers for triple negative breast cancer in Caucasian American women

“…SEPT7 along with SEPT2, cytoskeletal proteins evolutionary conserved from yeast to mammals, when silenced in MB231 cells, demonstrated inhibitory effects in cellular proliferation, apoptosis, migration, and invasion, strongly suggesting that SEPT7 is involved in breast carcinogenesis and can serve as therapeutic targets for highly invasive breast cancers [106]. IKBIP, a gene not commonly reported in cancer data, was recently shown to be highly involved in EMT and was associated with more aggressive phenotypes in gliomas [107]. Finally, down-regulation of TXNIP, demonstrated in breast, bladder, and gastric cancer was recently shown to be a common feature in human tumor xenograft models in which intra-tumoral leukocytes are responsible for the decreased expression of TXNIP, suggesting that TXNIP expression levels can be used to monitor the functional state of tumor-infiltrating leukocytes [108].…”

“…SEPT7 along with SEPT2, cytoskeletal proteins evolutionary conserved from yeast to mammals, when silenced in MB231 cells, demonstrated inhibitory effects in cellular proliferation, apoptosis, migration, and invasion, strongly suggesting that SEPT7 is involved in breast carcinogenesis and can serve as therapeutic targets for highly invasive breast cancers [106]. IKBIP, a gene not commonly reported in cancer data, was recently shown to be highly involved in EMT and was associated with more aggressive phenotypes in gliomas [107].…”