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.
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.
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DOI：
10.1371/journal.pone.0191581
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Prystowsky MB
中科院分区：
文献类型：
--
作者：
Anayannis NV;Schlecht NF;Ben-Dayan M;Smith RV;Belbin TJ;Ow TJ;Blakaj DM;Burk RD;Leonard SM;Woodman CB;Parish JL;Prystowsky MB
为了评估人乳头瘤病毒（HPV）阳性头颈部鳞状细胞癌中E2基因破坏与病毒基因表达和临床结果的关系，我们使用两种基于pcr的方法检测E2破坏，然后进行Sanger测序，评估了31例口咽癌和17例非口咽HPV16阳性癌。RT-qPCR还检测了HPV16 E6、E7和E2转录本以及细胞ARF和INK4A的表达。E2破坏、E2/E6/E7表达与临床结果之间的关系通过Kaplan-Meier分析评估局部区域复发和疾病特异性生存。大多数HPV16阳性口咽癌（n = 21,68%）具有完整的E2基因，而大多数HPV16阳性非口咽癌（n = 10,59%）具有破坏的E2基因。3例口咽肿瘤和2例非口咽肿瘤E2有缺失。在口咽肿瘤中检测完整的E2基因与更高的DNA病毒载量和E2/E6/E7、ARF和INK4A表达升高相关。与E2破坏的肿瘤相比，E2完整的口咽癌具有较低的局部区域复发风险（log-rank p = 0.04）和改善的疾病特异性生存（p = 0.03）。此外，E7高表达与局部区域复发风险较低相关（p = 0.004）， E6高表达与局部区域复发风险较低相关（p = 0.006）。总之，完整的E2基因在HPV16阳性口咽癌中比在非口咽癌中更常见；与E2基因破坏的口咽癌患者相比，完整E2基因的存在与更高的HPV病毒载量、更高的病毒癌基因表达和更好的临床结果相关。
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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影响因子：
8.4
作者：
Ferris, RL;Martinez, I;Khan, S
通讯作者：
Khan, S
影响因子：
51.1
作者：
Cogliano, V;Baan, R;El Ghissassi, F
通讯作者：
El Ghissassi, F
DOI：
10.1097/00004347-199804000-00009
发表时间：
1998-04-01
影响因子：
2.4
作者：
Kalantari, M;Karlsen, F;Johansson, B
通讯作者：
Johansson, B
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作者：
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通讯作者：
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影响因子：
4.7
作者：
Cheung, Jo L. K.;Cheung, Tak-Hong;Chan, Paul K. S.
通讯作者：
Chan, Paul K. S.