Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer.
Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer.
复制标题
DOI：
10.1186/s40364-020-00235-y
复制
发表时间：
2020
影响因子：
11.1
通讯作者：
Mineta H
中科院分区：
文献类型：
--
作者：
Misawa K;Yamada S;Mima M;Nakagawa T;Kurokawa T;Imai A;Mochizuki D;Shinmura D;Yamada T;Kita J;Ishikawa R;Yamaguchi Y;Misawa Y;Kanazawa T;Kawasaki H;Mineta H
迫切需要新的生物标志物来改善头颈部鳞状细胞癌（HNSCC）的个性化治疗方法。整体DNA低甲基化在多步骤癌变中具有广泛的功能，并且长散布核苷酸元件-1（LINE-1）的低甲基化与增加的反转录转座子活性和诱导的基因组不稳定性有关。然而，关于LINE-1低甲基化及其在HNSCC中的预后意义的信息很少。在这项研究中，我们使用定量实时甲基化和非甲基化PCR分析了317例原发性HNSCC组织和225对匹配的正常粘膜组织沿着5例口腔癌（OCC）循环肿瘤DNA（ctDNA）样本的LINE-1低甲基化水平。根据各种临床特征和预后影响进行分析。结果显示，同一个体的HNSCC组织中LINE-1低甲基化水平显著高于相应的正常组织（P < 0.001）。单因素分析显示，LINE-1低甲基化水平高与无病生存率（DFS;对数秩检验，P = 0.038）相关，而多因素分析表明，它们是DFS的重要独立预后因素（风险比：2.10，95%置信区间：1.02-4.36; P = 0.045）。此外，具有高LINE-1低甲基化水平的样品显示5-羟甲基胞嘧啶（5-hmC）水平的最大降低和肿瘤抑制基因甲基化指数的增加（分别为P = 0.006和P < 0.001）。此外，ctDNA研究还表明LINE-1低甲基化在OCC中具有较高的预测能力。LINE-1低甲基化与早期OCC复发的较高风险相关，因此是OCC的潜在预测生物标志物。此外，5-hmC水平也表现出预测OCC的潜力，基于其与LINE-1低甲基化水平的负相关性。因此，LINE-1低甲基化分析可用于确定患者预后和实时监测疾病复发，并可作为OCC筛查的替代方法。补充信息随附于10.1186/s40364-020-00235-y。
New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC. In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications. The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC. LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening. Supplementary information accompanies this paper at 10.1186/s40364-020-00235-y.
登录
查看更多内容
影响因子：
24.5
作者：
Hur K;Cejas P;Feliu J;Moreno-Rubio J;Burgos E;Boland CR;Goel A
通讯作者：
Goel A
影响因子：
6.4
作者：
Smith, Ian M.;Mydlarz, Wojciech K.;Califano, Joseph A.
通讯作者：
Califano, Joseph A.
影响因子：
5.7
作者：
Furlan C;Polesel J;Barzan L;Franchin G;Sulfaro S;Romeo S;Colizzi F;Rizzo A;Baggio V;Giacomarra V;Dei Tos AP;Boscolo-Rizzo P;Vaccher E;Dolcetti R;Sigalotti L;Fratta E
通讯作者：
Fratta E
影响因子：
--
作者：
Nagai, Yuzo;Sunami, Eiji;Watanabe, Toshiaki
通讯作者：
Watanabe, Toshiaki
影响因子：
3.9
作者：
Huang, Yuan;Wei, Ling;Qin, Yang
通讯作者：
Qin, Yang