The Clinical Analysis Of NFKBIA Polymorphism In Glioblastoma

Objective: Aberrant constitutive activation of nuclear factor-kappa B(NF-κB) has been observed in glioblastomas, while NF-κB inhibitor-α(NFKBIA) could inhibit NF-κB signaling pathway under severalphysiological processes. However, the contribution of NFKBIA toglioblastomas is poorly understood. Therefore, The aim of the present studywas to explore NFKBIA protein levels and their relationship with mRNAlevels, mutation and copy number variation of NFKBIA in glioblastomas.This will lay a foundation for further clarifying the role of NFKBIA in thedevelopment of glioblastomas.Methods: We analyzed24human glioblastoma samples and8samplesof non-cancerous brain tissue for mutations, copy number variation andexpression (protein and mRNA levels) of NFKBIA. We used PCRamplification and direct sequencing to detect mutaions of NFKBIA, WesternBlot to detect expression of NFKBIA protein, Real-time quantitative PCR todetect copy number variation and mRNA expression of NFKBIA.Results: We genotyped one single nucleotide polymorphism rs1957106in NFKBIA in glioblastomas. NFKBIA protein levels detected weresignificantly lower in glioblastomas harboring the rs1957106CT and TTgenotypes than in samples harboring the rs1957106CC genotype. Moreover,NFKBIA protein levels were significantly lower in glioblastomas harboringthe CC and CT genotypes than in non-cancerous brain tissues. NFKBIAmRNA levels were lower in glioblastomas compared with non-cancerous brain tissue. Furthermore, NFKBIA mRNA levels were significantly lower inglioblastomas harboring the rs1957106CT and TT genotypes than in samplesharboring the rs1957106CC genotype (CT/TT:0.31±0.11, CC:0.54±0.18,noncancerous:0.78±0.12, P<0.001). The relative copy number of NFKBIAwas significantly lower in7of the10glioblastomas, all of which had thers1957106CT and TT genotypes and low NFKBIA protein levels.Conclusions: The minor allele for one synonymous single nucleotidepolymorphism in NFKBIA, rs1957106, was associated with lower proteinexpression and lower copy number of NFKBIA.