Tingting Qin1, Lada A Koneva1,2, Yidan Liu1,3, Yanxiao Zhang1,4, Anna E Arthur5,6, Katie R Zarins5, Thomas E Carey7, Douglas Chepeha7,8, Gregory T Wolf7, Laura S Rozek5, Maureen A Sartor1. 1. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. 2. Kennedy Institute of Rheumatology, University of Oxford, United Kingdom. 3. Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 4. Ludwig Institute for Cancer Research, La Jolla, CA, USA. 5. Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA. 6. Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL, USA. 7. Department of Otolaryngology/Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA. 8. Department of Otolaryngology/Head & Neck Surgery, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: Human papillomavirus (HPV) oncogenes E6, E7, and shorter isoforms of E6 (E6*) are known carcinogenic factors in head and neck squamous cell carcinoma (HNSCC). Little is known regarding E6* functions. METHODS: We analyzed RNA-seq data from 68 HNSCC HPV type 16-positive tumors to determine host genes and pathways associated with E6+E7 expression (E6E7) or the percent of full-length E6 (E6%FL). Influence scores of E6E7 and E6%FL were used to test for associations with clinical variables. RESULTS: For E6E7, we recapitulated all major known affected pathways and revealed additional pathways. E6%FL was found to affect mitochondrial processes, and E6%FL influence score was significantly associated with overall survival and tumor size. CONCLUSIONS: HPV E6E7 and E6* result in extensive, dose-dependent compensatory effects and dysregulation of key cancer pathways. The switch from E6 to E6* promotes oxidative phosphorylation, larger tumor size, and worse prognosis, potentially serving as a prognostic factor for HPV-positive HNSCC.
BACKGROUND:Human papillomavirus (HPV) oncogenes E6, E7, and shorter isoforms of E6 (E6*) are known carcinogenic factors in head and neck squamous cell carcinoma (HNSCC). Little is known regarding E6* functions. METHODS: We analyzed RNA-seq data from 68 HNSCC HPV type 16-positive tumors to determine host genes and pathways associated with E6+E7 expression (E6E7) or the percent of full-length E6 (E6%FL). Influence scores of E6E7 and E6%FL were used to test for associations with clinical variables. RESULTS: For E6E7, we recapitulated all major known affected pathways and revealed additional pathways. E6%FL was found to affect mitochondrial processes, and E6%FL influence score was significantly associated with overall survival and tumor size. CONCLUSIONS:HPV E6E7 and E6* result in extensive, dose-dependent compensatory effects and dysregulation of key cancer pathways. The switch from E6 to E6* promotes oxidative phosphorylation, larger tumor size, and worse prognosis, potentially serving as a prognostic factor for HPV-positive HNSCC.
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