Gameiro Steven F, Ghasemi Farhad, Zeng Peter Y F, Mundi Neil, Howlett Christopher J, Plantinga Paul, Barrett John W, Nichols Anthony C, Mymryk Joe S
Department of Microbiology and Immunology, The University of Western Ontario, London, ON, N6A 3K7, Canada.
Department of Surgery, The University of Western Ontario, London, ON, N6A 3K7, Canada.
Infect Agent Cancer. 2021 Feb 15;16(1):13. doi: 10.1186/s13027-021-00347-6.
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.
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.
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.
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.
在头颈部鳞状细胞癌（HNSCC）中已观察到核受体结合SET结构域蛋白1（NSD1）基因频繁发生突变。NSD1编码一种组蛋白3赖氨酸-36甲基转移酶。尽管T细胞浸润较弱，但NSD1突变与人乳头瘤病毒阴性（HPV-）肿瘤的临床预后改善及对铂类化疗药物的敏感性增加相关。然而，NSD1及相关家族成员NSD2和NSD3在人乳头瘤病毒阳性（HPV+）HNSCC中的作用尚不清楚。
利用来自癌症基因组图谱（TCGA）的500多名HNSCC患者的数据，我们比较了HPV+和HPV- HNSCC中NSD1、NSD2和NSD3的mRNA表达相对水平。对HPV+和HPV- HNSCC中T细胞浸润与NSD1、NSD2和NSD3 mRNA表达相对水平进行相关性分析。此外，根据NSD1、NSD2和NSD3表达水平分层，比较了HPV+和HPV-患者亚组的总生存结果。
在HPV+ HNSCC中，NSD1、NSD2或NSD3的表达水平与淋巴细胞浸润改变无关。更重要的是，NSD1、NSD2或NSD3的低表达与HPV+而非HPV- HNSCC患者的总生存显著降低相关。
这些结果鲜明地说明了HPV+和HPV- HNSCC肿瘤分子特征的差异，并表明NSD1、NSD2和NSD3的表达水平应作为改善HPV+ HNSCC预后和患者分层的新临床指标进一步研究。
