Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis

Steven F Gameiro; Farhad Ghasemi; Peter Y F Zeng; Neil Mundi; Christopher J Howlett; Paul Plantinga; John W Barrett; Anthony C Nichols; Joe S Mymryk

doi:10.1186/s13027-021-00347-6

Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis

Infect Agent Cancer. 2021 Feb 15;16(1):13. doi: 10.1186/s13027-021-00347-6.

Authors

Steven F Gameiro^#¹, Farhad Ghasemi^#², Peter Y F Zeng³, Neil Mundi³, Christopher J Howlett⁴, Paul Plantinga⁴, John W Barrett³, Anthony C Nichols^{5

6

7

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9}, Joe S Mymryk^{10

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12

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14}

Affiliations

¹ Department of Microbiology and Immunology, The University of Western Ontario, London, ON, N6A 3K7, Canada.
² Department of Surgery, The University of Western Ontario, London, ON, N6A 3K7, Canada.
³ Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON, N6A 3K7, Canada.
⁴ Department of Pathology, The University of Western Ontario, London, ON, N6A 3K7, Canada.
⁵ Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON, N6A 3K7, Canada. Anthony.Nichols@lhsc.on.ca.
⁶ Department of Pathology, The University of Western Ontario, London, ON, N6A 3K7, Canada. Anthony.Nichols@lhsc.on.ca.
⁷ Department of Oncology, The University of Western Ontario, London, ON, N6A 3K7, Canada. Anthony.Nichols@lhsc.on.ca.
⁸ London Regional Cancer Program, Lawson Health Research Institute, London, ON, N6C 2R5, Canada. Anthony.Nichols@lhsc.on.ca.
⁹ Department of Otolaryngology - Head and Neck Surgery, Schulich School of Medicine & Dentistry, Western University, Room B3-431A, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. Anthony.Nichols@lhsc.on.ca.
¹⁰ Department of Microbiology and Immunology, The University of Western Ontario, London, ON, N6A 3K7, Canada. jmymryk@uwo.ca.
¹¹ Department of Otolaryngology, Head & Neck Surgery, The University of Western Ontario, London, ON, N6A 3K7, Canada. jmymryk@uwo.ca.
¹² Department of Oncology, The University of Western Ontario, London, ON, N6A 3K7, Canada. jmymryk@uwo.ca.
¹³ London Regional Cancer Program, Lawson Health Research Institute, London, ON, N6C 2R5, Canada. jmymryk@uwo.ca.
¹⁴ London Regional Cancer Program, 790 Commissioners Rd. East, London, Ontario, N6A 4L6, Canada. jmymryk@uwo.ca.

^# Contributed equally.

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.

Keywords: Epigenetics; HPV; Head and neck cancer; Head and neck squamous cell carcinoma; Histone methyltransferase; The Cancer Genome Atlas; WHSC1; WHSC1L1.

Abstract

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