1. Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis.
- Author
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Gameiro, Steven F., Ghasemi, Farhad, Zeng, Peter Y. F., Mundi, Neil, Howlett, Christopher J., Plantinga, Paul, Barrett, John W., Nichols, Anthony C., and Mymryk, Joe S.
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CANCER patients , *CARRIER proteins , *STATISTICAL correlation , *GENE expression , *HUMAN genome , *MESSENGER RNA , *HEAD & neck cancer , *PAPILLOMAVIRUS diseases , *SQUAMOUS cell carcinoma , *SURVIVAL analysis (Biometry) , *BIBLIOGRAPHIC databases , *NUCLEAR proteins , *EPIGENOMICS , *DISEASE complications - Abstract
Background: Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear. Methods: Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels. Results: Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC. Conclusion: These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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