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.
Highlights
Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are infiltrative brain tumors that include astrocytomas, oligoastrocytomas and oligodendrogliomas[1]
Treatment with nanoparticles loaded with recombinant Iκ Bα and curcumin, a natural polyphenol that inhibits the phosphorylation of Iκ Bα, has been shown to decrease the expression of NFκ B target genes such as CCND1, CCNE1, BCL2L1 and COX2, thereby inducing apoptotic cell death in a glioblastoma cell line[17]
Previous studies have suggested a correlation between the levels of phospho-Iκ Bα and the grade of gliomas[15]; to the best of our knowledge, there is no available data assessing the biological and clinical implications of NFKBIA dosage and expression in LGGs
Summary
Lower-grade gliomas (LGGs), which are uniformly fatal in young adults, are infiltrative brain tumors that include astrocytomas, oligoastrocytomas and oligodendrogliomas[1]. In addition to traditional morphological histopathology, detailed molecular classification of gliomas contributes to the WHO grading schemes and will be incorporated into a new integrated diagnosis scheme[3,4,5] In this sense, molecular pathology will contribute to the stratification of patients in treatment-specific subgroups, which will lead to the development of more personalized and biologically grounded therapies[6,7]. Given the potential role of NFKBIA in glioblastoma development and progression[15,16,17], we aimed to investigate, in LGGs, the impact of NFKBIA dosage and expression on patient survival, overall malignancy and the downstream activation of NFκ B
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
