Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Martin A Prusinkiewicz; Steven F Gameiro; Farhad Ghasemi; Mackenzie J Dodge; Peter Y F Zeng; Hanna Maekebay; John W Barrett; Anthony C Nichols; Joe S Mymryk

doi:10.3390/cancers12010253

Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Cancers (Basel). 2020 Jan 20;12(1):253. doi: 10.3390/cancers12010253.

Authors

Martin A Prusinkiewicz¹, Steven F Gameiro¹, Farhad Ghasemi², Mackenzie J Dodge¹, Peter Y F Zeng³, Hanna Maekebay¹, John W Barrett³, Anthony C Nichols^{3

4

5}, Joe S Mymryk^{1

3

4

5}

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 Oncology, The University of Western Ontario, London, ON N6A 3K7, Canada.
⁵ London Regional Cancer Program, Lawson Health Research Institute, London, ON N6C 2R5, Canada.

Abstract

Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact of HPV status on HNSCC metabolism remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique to HPV-positive HNSCC influences patient survival. The Cancer Genome Atlas RNA-seq data from primary HNSCC patient samples were categorized as 73 HPV-positive, 442 HPV-negative, and 43 normal-adjacent control tissues. We analyzed 229 metabolic genes and identified numerous differentially expressed genes between HPV-positive and negative HNSCC patients. HPV-positive carcinomas exhibited lower expression levels of genes involved in glycolysis and higher levels of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and β-oxidation than the HPV-negative carcinomas. Importantly, reduced expression of the metabolism-related genes SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, and SLC16A2 were correlated with improved patient survival only in the HPV-positive group. This work suggests that specific transcriptional alterations in metabolic genes may serve as predictive biomarkers of patient outcome and identifies potential targets for novel therapeutic intervention in HPV-positive head and neck cancers.

Keywords: TCGA; cancer metabolism; cellular respiration; glycolysis; head and neck cancer; human papillomavirus.

Abstract

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