Deletion and low expression of NFKBIA are associated with poor prognosis in lower-grade glioma patients

Autor(es)

Kinker, Gabriela Sarti ^[1] ; Thomas, Andrew Maltez ^{[2, 3, 4]} ; Carvalho, Vinicius Jardim ^{[3, 5]} ; Lima, Felipe Prata ^{[2, 3, 6]} ; Fujita, Andre ^[7]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Physiol, Inst Biosci, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Bioinformat Grad Program, Sao Paulo - Brazil

^[4] AC Camargo Canc Ctr, Int Res Ctr, Med Genom Lab, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst Biosci, Dept Bot, Sao Paulo - Brazil

^[6] Fed Inst Alagoas, Alagoas - Brazil

^[7] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 6, APR 7 2016.
• Citações Web of Science: 4

Resumo

Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are classified as grades II-III tumors according to their histological features. The NF kappa B transcription factor, a crucial player in cancer initiation and progression, is inactivated in the cytoplasm by inhibitory proteins (I kappa Bs) 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 I kappa B alpha, 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 NF kappa B activation. Overall, the present findings reveal the prognostic value of NFKBIA in LGGs, reinforcing the relevance of NF kappa B signaling in the development and progression of gliomas. (AU)

• Processo FAPESP: 15/01507-7 - Investigação de perfis microbianos humanos e sua relação com o câncer
• Beneficiário: Andrew Maltez Thomas
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/27287-0 - Caracterização do sistema melatonérgico de gliomas humanos e sua implicação sobre o grau de agressividade e invasibilidade tumoral
• Beneficiário: Gabriela Sarti Kinker
• Linha de fomento: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/03447-6 - Estruturas combinatórias, otimização e algoritmos em Teoria da Computação
• Beneficiário: Carlos Eduardo Ferreira
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/09576-5 - Desenvolvimento de técnicas estatístico-computacionais para construir, modelar e analisar redes biológicas envolvidas em doenças humanas
• Beneficiário: André Fujita
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/01587-0 - Armazenagem, modelagem e análise de sistemas dinâmicos para aplicações em e-Science
• Beneficiário: João Eduardo Ferreira
• Linha de fomento: Auxílio à Pesquisa - Programa eScience e Data Science - Temático