A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia: observation from a prospective study.
A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia: observation from a prospective study.
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P16羟甲基化和真甲基化对口腔上皮不典型增生恶性转化预测的相似作用：前瞻性研究观察
DOI：
10.1186/s12885-018-4787-6
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发表时间：
2018-09-24
期刊：
影响因子：
3.8
通讯作者：
Deng D
中科院分区：
文献类型：
--
作者：
Liu H;Liu Z;Liu XW;Xu S;Wang L;Liu Y;Zhou J;Gu L;Gao Y;Liu XY;Shi H;Sun Z;Deng D
背景：总P16甲基化（P16M），包括P16羟甲基化（P16H）和真P16M，与口腔上皮发育不良（OED）的恶性转化相关。true-P16M和P16H都是癌变的早期事件。本研究的目的是前瞻性地确定是否需要区分真p16m和P16H来预测oed的癌症发展。方法：将265例轻度或中度OED患者纳入双盲双中心队列。Total-P16M和P16H采用115 bp MethyLight、tet辅助亚硫酸盐（TAB）甲基化特异性PCR （MSP）和TAB测序进行分析。总p16m阳性和p16h阴性样品定义为真p16m阳性。在至少24个月的随访期间监测oed的进展情况。结果：73例总p16m阳性oed中23例（31.5%）检出P16H。随访247例患者，最终依从率为93.2%。在随访期间（中位41.0个月），13.0%（32/247）的患者观察到ed衍生的鳞状细胞癌。与总p16m阴性患者相比，总p16m阳性患者的癌症进展率显著增加[23.3% vs 8.6%；校正优势比= 2.67 (95% CI: 1.19-5.99)]。然而，P16H-和真p16m阳性oed的癌症进展率相似，分别为26.1%（6/23）和22.0% (11/50)；优势比= 0.80 (95% CI: 0.22-2.92)]。这些患者的无癌生存率也相似。结论：P16H和true-P16M是判断oed恶性潜能的相似生物标志物。区分P16H和真p16m，至少在OED中，在临床应用中可能没有必要。试验注册：本研究已在美国国立卫生研究院临床试验方案注册系统（试验编号bernct02967120，可在https://ClinicalTrials.gov/ct2/show/NCT02967120上获得）进行前瞻性注册。
Background:Total P16 methylation (P16M), including P16 hydroxymethylation (P16H) and true-P16M, correlates with malignant transformation of oral epithelial dysplasia (OED). Both true-P16M and P16H are early events in carcinogenesis. The aim of this study is to prospectively determine if discrimination of true-P16M from P16H is necessary for prediction of cancer development from OEDs.Methods:Patients (n = 265) with mild or moderate OED were recruited into the double blind two-center cohort. Total-P16M and P16H were analyzed using the 115-bp MethyLight, TET-assisted bisulfite (TAB) methylation-specific PCR (MSP), and TAB-sequencing. Total-P16M-positive and P16H-negative samples were defined as true-P16M-positive. Progression of OEDs was monitored for a minimum 24 months follow-up period.Results:P16H was detected in 23 of 73 (31.5%) total-P16M-positive OEDs. Follow-up information was obtained from 247 patients with an ultimate compliance rate of 93.2%. OED-derived squamous cell carcinomas were observed in 13.0% (32/247) patients during follow-up (median, 41.0 months). The cancer progression rate for total-P16M-positive patients was significantly increased when compared to total-P16M-negative patients [23.3% vs 8.6%; adjusted odds ratio = 2.67 (95% CI: 1.19-5.99)]. However, the cancer progression rates were similar between P16H- and true-P16M-positive OEDs [26.1% (6/23) vs 22.0% (11/50); odds ratio = 0.80 (95% CI: 0.22-2.92)]. The cancer-free survival was also similar for these patients.Conclusion:P16H and true-P16M are similar biomarkers for determining malignant potential of OEDs. Discrimination of P16H from true-P16M, at least in OED, may be not necessary in clinical applications.Trial registration:This study is registered prospectively in the U.S. National Institutes of Health Clinical Trials Protocol Registration System (trial numberNCT02967120, available at https://ClinicalTrials.gov/ct2/show/NCT02967120 ).
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.9
作者：
Kannengiesser, Caroline;Brookes, Sharon;Bressac-de Paillerets, Brigitte
通讯作者：
Bressac-de Paillerets, Brigitte
ANRIL 和 P16 基因的协调转录因 P16 DNA 甲基化而沉默。
影响因子：
5.1
作者：
Gan, Ying;Ma, Wanru;Deng, Dajun
通讯作者：
Deng, Dajun
癌细胞中等位基因特异性 p16 甲基化的稳态维持，伴有动态局部甲基化和羟甲基化
影响因子：
3.7
作者：
Qin S;Li Q;Zhou J;Liu ZJ;Su N;Wilson J;Lu ZM;Deng D
通讯作者：
Deng D