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Significant association between host transcriptome‐derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer
dc.contributor.authorQin, Tingting
dc.contributor.authorKoneva, Lada A.
dc.contributor.authorLiu, Yidan
dc.contributor.authorZhang, Yanxiao
dc.contributor.authorArthur, Anna E.
dc.contributor.authorZarins, Katie R.
dc.contributor.authorCarey, Thomas E
dc.contributor.authorChepeha, Douglas
dc.contributor.authorWolf, Gregory T.
dc.contributor.authorRozek, Laura S.
dc.contributor.authorSartor, Maureen A.
dc.date.accessioned2020-09-02T14:58:39Z
dc.date.availableWITHHELD_13_MONTHS
dc.date.available2020-09-02T14:58:39Z
dc.date.issued2020-09
dc.identifier.citationQin, Tingting; Koneva, Lada A.; Liu, Yidan; Zhang, Yanxiao; Arthur, Anna E.; Zarins, Katie R.; Carey, Thomas E; Chepeha, Douglas; Wolf, Gregory T.; Rozek, Laura S.; Sartor, Maureen A. (2020). "Significant association between host transcriptome‐derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer." Head & Neck 42(9): 2375-2389.
dc.identifier.issn1043-3074
dc.identifier.issn1097-0347
dc.identifier.urihttps://hdl.handle.net/2027.42/156432
dc.description.abstractBackgroundHuman 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.MethodsWe 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.ResultsFor 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.ConclusionsHPV 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.
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherhuman papillomavirus
dc.subject.otherinfluence score
dc.subject.othersurvival
dc.subject.otherE6
dc.subject.otherE6*
dc.subject.otherE7
dc.subject.otherhead and neck cancer
dc.titleSignificant association between host transcriptome‐derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbsecondlevelOtolaryngology
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/156432/2/hed26244.pdfen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/156432/1/hed26244_am.pdfen_US
dc.identifier.doi10.1002/hed.26244
dc.identifier.sourceHead & Neck
dc.identifier.citedreferenceCancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015; 517 ( 7536 ): 576 ‐ 582.
dc.identifier.citedreferenceChung CH, Gillison ML. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 2009; 15 ( 22 ): 6758 ‐ 6762.
dc.identifier.citedreferenceFilippova M, Johnson MM, Bautista M, et al. The large and small isoforms of human papillomavirus type 16 E6 bind to and differentially affect procaspase 8 stability and activity. J Virol. 2007; 81 ( 8 ): 4116 ‐ 4129.
dc.identifier.citedreferenceKoneva LA, Zhang Y, Virani S, et al. HPV integration in HNSCC correlates with survival outcomes, immune response signatures, and candidate drivers. Mol Cancer Res. 2018; 16 ( 1 ): 90 ‐ 102.
dc.identifier.citedreferenceKim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013; 14 ( 4 ): R36.
dc.identifier.citedreferenceAndrews S. FastQC: a quality control tool for high throughput sequence data. 2010; http://www.bioinformatics.babraham.ac.uk/projects/fastqc.
dc.identifier.citedreferenceWang L, Wang S, Li W. RSeQC: quality control of RNA‐seq experiments. Bioinformatics. 2012; 28 ( 16 ): 2184 ‐ 2185.
dc.identifier.citedreferenceAnders S, Pyl PT, Huber W. HTSeq—a Python framework to work with high‐throughput sequencing data. Bioinformatics. 2015; 31 ( 2 ): 166 ‐ 169.
dc.identifier.citedreferenceRitchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for RNA‐sequencing and microarray studies. Nucleic Acids Res. 2015; 43 ( 7 ): e47.
dc.identifier.citedreferenceDobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA‐seq aligner. Bioinformatics. 2013; 29 ( 1 ): 15 ‐ 21.
dc.identifier.citedreferenceNguyen Y, Nettleton D, Liu H, Tuggle CK. Detecting differentially expressed genes with RNA‐seq data using backward selection to account for the effects of relevant covariates. J Agric Biol Environ Stat. 2015; 20 ( 4 ): 577 ‐ 597.
dc.identifier.citedreferenceWilliams VM, Filippova M, Soto U, Duerksen‐Hughes PJ. HPV‐DNA integration and carcinogenesis: putative roles for inflammation and oxidative stress. Future Virol. 2011; 6 ( 1 ): 45 ‐ 57.
dc.identifier.citedreferenceLee C, Patil S, Sartor MA. RNA‐enrich: a cut‐off free functional enrichment testing method for RNA‐seq with improved detection power. Bioinformatics. 2016; 32 ( 7 ): 1100 ‐ 1102.
dc.identifier.citedreferenceCarson M. GO.db: a set of annotation maps describing the entire Gene Ontology. R package version 3.7.0. 2018.
dc.identifier.citedreferenceLuo W, Brouwer C. Pathview: an R/bioconductor package for pathway‐based data integration and visualization. Bioinformatics. 2013; 29 ( 14 ): 1830 ‐ 1831.
dc.identifier.citedreferenceSchacht T, Oswald M, Eils R, Eichmuller SB, Konig R. Estimating the activity of transcription factors by the effect on their target genes. Bioinformatics. 2014; 30 ( 17 ): i401 ‐ i407.
dc.identifier.citedreferenceTherneau T. A package for survival analysis in S. version 2.38. 2015.
dc.identifier.citedreferenceKassambara A, Kosinski M, Biecek P, Fabian S. survminer: drawing survival curves using ’ggplot2’. R package version 0.4.3. 2018.
dc.identifier.citedreferenceStadler ME, Patel MR, Couch ME, Hayes DN. Molecular biology of head and neck cancer: risks and pathways. Hematol Oncol Clin North Am. 2008; 22 ( 6 ): 1099 ‐ 1124. vii.
dc.identifier.citedreferenceThomas M, Pim D, Banks L. The role of the E6‐p53 interaction in the molecular pathogenesis of HPV. Oncogene. 1999; 18 ( 53 ): 7690 ‐ 7700.
dc.identifier.citedreferenceWanichwatanadecha P, Sirisrimangkorn S, Kaewprag J, Ponglikitmongkol M. Transactivation activity of human papillomavirus type 16 E6*I on aldo‐keto reductase genes enhances chemoresistance in cervical cancer cells. J Gen Virol. 2012; 93 ( Pt 5 ): 1081 ‐ 1092.
dc.identifier.citedreferenceCricca M, Venturoli S, Leo E, Costa S, Musiani M, Zerbini M. Molecular analysis of HPV 16 E6I/E6II spliced mRNAs and correlation with the viral physical state and the grade of the cervical lesion. J Med Virol. 2009; 81 ( 7 ): 1276 ‐ 1282.
dc.identifier.citedreferenceFunk JO, Waga S, Harry JB, Espling E, Stillman B, Galloway DA. Inhibition of CDK activity and PCNA‐dependent DNA replication by p21 is blocked by interaction with the HPV‐16 E7 oncoprotein. Genes Dev. 1997; 11 ( 16 ): 2090 ‐ 2100.
dc.identifier.citedreferenceJones DL, Alani RM, Munger K. The human papillomavirus E7 oncoprotein can uncouple cellular differentiation and proliferation in human keratinocytes by abrogating p21Cip1‐mediated inhibition of cdk2. Genes Dev. 1997; 11 ( 16 ): 2101 ‐ 2111.
dc.identifier.citedreferenceSpardy N, Covella K, Cha E, et al. Human papillomavirus 16 E7 oncoprotein attenuates DNA damage checkpoint control by increasing the proteolytic turnover of claspin. Cancer Res. 2009; 69 ( 17 ): 7022 ‐ 7029.
dc.identifier.citedreferenceKutler DI, Auerbach AD, Satagopan J, et al. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg. 2003; 129 ( 1 ): 106 ‐ 112.
dc.identifier.citedreferenceQin T, Zhang Y, Zarins KR, et al. Expressed HNSCC variants by HPV‐status in a well‐characterized Michigan cohort. Sci Rep. 2018; 8 ( 1 ): 11458.
dc.identifier.citedreferenceAshton TM, McKenna WG, Kunz‐Schughart LA, Higgins GS. Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 2018; 24 ( 11 ): 2482 ‐ 2490.
dc.identifier.citedreferenceReznik E, Miller ML, Senbabaoglu Y, et al. Mitochondrial DNA copy number variation across human cancers. Elife. 2016; 5: e10769. https://doi.org/10.7554/eLife.10769.
dc.identifier.citedreferenceKraft CS, LeMoine CM, Lyons CN, Michaud D, Mueller CR, Moyes CD. Control of mitochondrial biogenesis during myogenesis. Am J Physiol Cell Physiol. 2006; 290 ( 4 ): C1119 ‐ C1127.
dc.identifier.citedreferenceChen CT, Shih YR, Kuo TK, Lee OK, Wei YH. Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells. Stem Cells. 2008; 26 ( 4 ): 960 ‐ 968.
dc.identifier.citedreferenceHong A, Zhang X, Jones D, et al. E6 viral protein ratio correlates with outcomes in human papillomavirus related oropharyngeal cancer. Cancer Biol Ther. 2016; 17 ( 2 ): 181 ‐ 187.
dc.identifier.citedreferencede Boer MA, Jordanova ES, Kenter GG, et al. High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patients. Clin Cancer Res. 2007; 13 ( 1 ): 132 ‐ 138.
dc.identifier.citedreferenceWestra WH. The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Head Neck Pathol. 2009; 3 ( 1 ): 78 ‐ 81.
dc.identifier.citedreferenceChiang C, Pauli EK, Biryukov J, et al. The human papillomavirus E6 oncoprotein targets USP15 and TRIM25 to suppress RIG‐I‐mediated innate immune signaling. J Virol. 2018; 92 ( 6 ):pii: e01737‐17. https://doi.org/10.1128/JVI.01737-17.
dc.identifier.citedreferenceMunger K, Werness BA, Dyson N, Phelps WC, Harlow E, Howley PM. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J. 1989; 8 ( 13 ): 4099 ‐ 4105.
dc.identifier.citedreferenceVande Pol SB, Klingelhutz AJ. Papillomavirus E6 oncoproteins. Virology. 2013; 445 ( 1–2 ): 115 ‐ 137.
dc.identifier.citedreferenceScheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990; 63 ( 6 ): 1129 ‐ 1136.
dc.identifier.citedreferenceMoody CA, Laimins LA. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer. 2010; 10 ( 8 ): 550 ‐ 560.
dc.identifier.citedreferenceNees M, Geoghegan JM, Hyman T, Frank S, Miller L, Woodworth CD. Papillomavirus type 16 oncogenes downregulate expression of interferon‐responsive genes and upregulate proliferation‐associated and NF‐kappaB‐responsive genes in cervical keratinocytes. J Virol. 2001; 75 ( 9 ): 4283 ‐ 4296.
dc.identifier.citedreferenceRonco LV, Karpova AY, Vidal M, Howley PM. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor‐3 and inhibits its transcriptional activity. Genes Dev. 1998; 12 ( 13 ): 2061 ‐ 2072.
dc.identifier.citedreferencePark JS, Kim EJ, Kwon HJ, Hwang ES, Namkoong SE, Um SJ. Inactivation of interferon regulatory factor‐1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7‐mediated immune evasion mechanism in cervical carcinogenesis. J Biol Chem. 2000; 275 ( 10 ): 6764 ‐ 6769.
dc.identifier.citedreferenceBello JO, Nieva LO, Paredes AC, Gonzalez AM, Zavaleta LR, Lizano M. Regulation of the Wnt/beta‐catenin signaling pathway by human papillomavirus E6 and E7 oncoproteins. Viruses. 2015; 7 ( 8 ): 4734 ‐ 4755.
dc.identifier.citedreferenceBodily JM, Mehta KP, Laimins LA. Human papillomavirus E7 enhances hypoxia‐inducible factor 1‐mediated transcription by inhibiting binding of histone deacetylases. Cancer Res. 2011; 71 ( 3 ): 1187 ‐ 1195.
dc.identifier.citedreferenceDuensing S, Munger K. The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res. 2002; 62 ( 23 ): 7075 ‐ 7082.
dc.identifier.citedreferenceKatzenellenbogen RA, Egelkrout EM, Vliet‐Gregg P, Gewin LC, Gafken PR, Galloway DA. NFX1‐123 and poly(A) binding proteins synergistically augment activation of telomerase in human papillomavirus type 16 E6‐expressing cells. J Virol. 2007; 81 ( 8 ): 3786 ‐ 3796.
dc.identifier.citedreferenceAlfandari J, Shnitman Magal S, Jackman A, Schlegel R, Gonen P, Sherman L. HPV16 E6 oncoprotein inhibits apoptosis induced during serum‐calcium differentiation of foreskin human keratinocytes. Virology. 1999; 257 ( 2 ): 383 ‐ 396.
dc.identifier.citedreferenceRosenberger S, De‐Castro Arce J, Langbein L, Steenbergen RD, Rosl F. Alternative splicing of human papillomavirus type‐16 E6/E6* early mRNA is coupled to EGF signaling via Erk1/2 activation. Proc Natl Acad Sci USA. 2010; 107 ( 15 ): 7006 ‐ 7011.
dc.identifier.citedreferenceSchneider‐Gadicke A, Schwarz E. Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes. EMBO J. 1986; 5 ( 9 ): 2285 ‐ 2292.
dc.identifier.citedreferenceZhang Y, Koneva LA, Virani S, et al. Subtypes of HPV‐positive head and neck cancers are associated with HPV characteristics, copy number alterations, PIK3CA mutation, and pathway signatures. Clin Cancer Res. 2016; 22: 4735 ‐ 4745.
dc.identifier.citedreferenceTang S, Tao M, McCoy JP Jr, Zheng ZM. The E7 oncoprotein is translated from spliced E6*I transcripts in high‐risk human papillomavirus type 16‐ or type 18‐positive cervical cancer cell lines via translation reinitiation. J Virol. 2006; 80 ( 9 ): 4249 ‐ 4263.
dc.identifier.citedreferencePim D, Banks L. HPV‐18 E6*I protein modulates the E6‐directed degradation of p53 by binding to full‐length HPV‐18 E6. Oncogene. 1999; 18 ( 52 ): 7403 ‐ 7408.
dc.identifier.citedreferenceWilliams VM, Filippova M, Filippov V, Payne KJ, Duerksen‐Hughes P. Human papillomavirus type 16 E6* induces oxidative stress and DNA damage. J Virol. 2014; 88 ( 12 ): 6751 ‐ 6761.
dc.identifier.citedreferencePsyrri A, DiMaio D. Human papillomavirus in cervical and head‐and‐neck cancer. Nat Clin Pract Oncol. 2008; 5 ( 1 ): 24 ‐ 31.
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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