title: Deletion and low expression of NFKBIA are associated with poor prognosis in lower-grade glioma patients.
abstract: Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are classified as grades II-III tumors according to their histological features. The NFκB transcription factor, a crucial player in cancer initiation and progression, is inactivated in the cytoplasm by inhibitory proteins (IκBs) that have been shown to exert tumor-suppressor activity. Therefore, using The Cancer Genome Atlas copy number alteration and RNA-Seq data from 398 patients, we evaluated the association between the expression and dosage of NFKBIA, which encodes IκBα, and the overall malignancy of LGGs. Deletion and low expression of NFKBIA were associated with enhanced tumor aggressiveness and poor prognosis in LGGs. Accordingly, the dosage and expression of NFKBIA were independent prognostic factors for 5-year survival (dosage: P = 0.016; expression: P = 0.002) and 5-year recurrence-free survival (dosage: P = 0.009; expression: P = 0.005). Moreover, gene set enrichment analyses and co-expression network analyses indicated a role for NFKBIA in the negative regulation of cell proliferation, possibly through the modulation of downstream NFκB activation. Overall, the present findings reveal the prognostic value of NFKBIA in LGGs, reinforcing the relevance of NFκB signaling in the development and progression of gliomas.
authors.affiliation: Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
authors.forename: Gabriela Sarti
authors.initials: GS
authors.lastname: Kinker
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.|Bioinformatics Graduate Program,University of São Paulo, São Paulo, Brazil.|Medical Genomics Laboratory, International Research Center, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Andrew Maltez
authors.initials: AM
authors.lastname: Thomas
authors.affiliation: Bioinformatics Graduate Program,University of São Paulo, São Paulo, Brazil.|Department of Botany, Institute of Bioscience, University of São Paulo, São Paulo, Brazil.
authors.forename: Vinicius Jardim
authors.initials: VJ
authors.lastname: Carvalho
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.|Bioinformatics Graduate Program,University of São Paulo, São Paulo, Brazil.|Federal Institute of Alagoas, Alagoas, Brazil.
authors.forename: Felipe Prata
authors.initials: FP
authors.lastname: Lima
authors.affiliation: Department of Computer Science, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics* / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D060787:Neoplasm Grading; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha