Genomic and transcriptomic profiling reveals prognostic nucleoporin alterations in head and neck squamous cell carcinoma
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Abstract
Objective: To characterize the mutational and expression landscape of nucleoporin (NUP) genes and evaluate their prognostic significance in head and neck squamous cell carcinoma (HNSCC).
Methods: This retrospective bioinformatic cross-sectional study utilized publicly available data from The Cancer Genome Atlas (TCGA). Thirty-eight nucleoporin genes were identified using the Human Genome Organisation Gene Nomenclature Committee database and relevant literature. Genomic alterations were analyzed in the TCGA HNSCC PanCancer Atlas cohort (n=523) using cBioPortal. Gene expression profiles were evaluated in the TCGA HNSC cohort (n=564) through the UCSC Xena platform. Overall survival was assessed in 500 HNSCC patients using Kaplan–Meier Plotter. Statistical significance was set at p<0.05.
Results: Genetic alterations in nucleoporin genes were identified in 41.1% of HNSCC cases. POM121L12 exhibited the highest alteration frequency (8%), followed by NUP155 (6%). Differential expression analysis revealed significant upregulation of NUP37, NUP62, NUP62CL, NUP85, NUP107, and NUP155, whereas SEC13, RANBP2, and DDX19B were significantly downregulated. Survival analysis demonstrated that elevated expression of NUP37 (HR=1.33, 95% CI: 1.02–1.75; p=0.037) and NUP54 (HR=1.31, 95% CI: 1.00–1.71; p=0.050) was associated with poorer overall survival. Conversely, increased NUP210L expression was associated with improved survival (HR=0.75, 95% CI: 0.57–0.98; p=0.031).
Conclusion: Nucleoporin genes exhibit frequent genomic and transcriptomic dysregulation in HNSCC. NUP37, NUP54, and NUP210L emerged as potential prognostic biomarkers, highlighting the nuclear pore complex as a promising target for future mechanistic and therapeutic investigations.
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Funding data
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Higher Education Commision, Pakistan
Grant numbers Project No. 15647 -
Khyber Medical University
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