دورية أكاديمية

Association of an intact E2 gene with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome in HPV16 positive head and neck squamous cell carcinoma.

التفاصيل البيبلوغرافية
العنوان: Association of an intact E2 gene with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome in HPV16 positive head and neck squamous cell carcinoma.
المؤلفون: Anayannis NV; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America., Schlecht NF; Department of Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Medicine (Oncology), Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, United States of America., Ben-Dayan M; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America., Smith RV; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America., Belbin TJ; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Discipline of Oncology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada., Ow TJ; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America., Blakaj DM; The James Cancer Center, Ohio State University, Columbus, OH, United States of America., Burk RD; Department of Epidemiology & Population Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Pediatrics (Genetics), Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Microbiology & Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.; Department of Obstetrics, Gynecology & Women's Health, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America., Leonard SM; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom., Woodman CB; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom., Parish JL; Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom., Prystowsky MB; Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, United States of America.
المصدر: PloS one [PLoS One] 2018 Feb 16; Vol. 13 (2), pp. e0191581. Date of Electronic Publication: 2018 Feb 16 (Print Publication: 2018).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Oncogenes* , Viral Load*, Alphapapillomavirus/*isolation & purification , Carcinoma, Squamous Cell/*therapy , DNA-Binding Proteins/*genetics , Head and Neck Neoplasms/*therapy , Oncogene Proteins, Viral/*genetics, Alphapapillomavirus/genetics ; Carcinoma, Squamous Cell/virology ; Female ; Head and Neck Neoplasms/virology ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Polymerase Chain Reaction ; Squamous Cell Carcinoma of Head and Neck
مستخلص: To assess the relationship of E2 gene disruption with viral gene expression and clinical outcome in human papillomavirus (HPV) positive head and neck squamous cell carcinoma, we evaluated 31 oropharyngeal and 17 non-oropharyngeal HPV16 positive carcinomas using two PCR-based methods to test for disruption of E2, followed by Sanger sequencing. Expression of HPV16 E6, E7 and E2 transcripts, along with cellular ARF and INK4A, were also assessed by RT-qPCR. Associations between E2 disruption, E2/E6/E7 expression, and clinical outcome were evaluated by Kaplan-Meier analysis for loco-regional recurrence and disease-specific survival. The majority (n = 21, 68%) of HPV16 positive oropharyngeal carcinomas had an intact E2 gene, whereas the majority of HPV16 positive non-oropharyngeal carcinomas (n = 10, 59%) had a disrupted E2 gene. Three of the oropharyngeal tumors and two of the non-oropharyngeal tumors had deletions within E2. Detection of an intact E2 gene was associated with a higher DNA viral load and increased E2/E6/E7, ARF and INK4A expression in oropharyngeal tumors. Oropharyngeal carcinomas with an intact E2 had a lower risk of loco-regional recurrence (log-rank p = 0.04) and improved disease-specific survival (p = 0.03) compared to tumors with disrupted E2. In addition, high E7 expression was associated with lower risk of loco-regional recurrence (p = 0.004) as was high E6 expression (p = 0.006). In summary, an intact E2 gene is more common in HPV16 positive oropharyngeal than non-oropharyngeal carcinomas; the presence of an intact E2 gene is associated with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome compared to patients with a disrupted E2 gene in oropharyngeal cancer.
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معلومات مُعتمدة: MR/N023498/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (DNA-Binding Proteins)
0 (E2 protein, Human papillomavirus type 16)
0 (Oncogene Proteins, Viral)
تواريخ الأحداث: Date Created: 20180217 Date Completed: 20180319 Latest Revision: 20231112
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5815588
DOI: 10.1371/journal.pone.0191581
PMID: 29451891
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0191581