Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma.
Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma.
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基于七 CpG 的预后特征与基因表达相结合可预测口腔鳞状细胞癌的生存
DOI：
10.1186/s13148-017-0392-9
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发表时间：
2017
影响因子：
5.7
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Shen S;Wang G;Shi Q;Zhang R;Zhao Y;Wei Y;Chen F;Christiani DC
DNA甲基化通过识别多种癌症的关键生物标志物，包括口腔鳞状细胞癌（OSCC），最常见的头颈部鳞状细胞癌，开始了基因组学生物学的最新革命。一个多阶段的筛选策略被用来确定DNA甲基化为基础的签名为口腔鳞癌的预后。我们使用癌症基因组图谱（TCGA）数据作为训练集，这些数据在来自基因表达综合数据库（GEO）的两个独立数据集中进行了验证。探讨DNA甲基化与相应基因表达的相关性及基因表达的预后价值。7个DNA甲基化CpG位点被鉴定出与OSCC总生存率显著相关。预后标志，7个CpG位点的加权线性组合，成功区分了OSCC患者的总生存期，并对生存期具有中等预测能力[训练集：风险比（HR）= 3.23，P = 5.52 × 10 - 10，曲线下面积（AUC）= 0.76;验证集1：HR = 2.79，P = 0.010，AUC = 0.67;验证集2：HR = 3.69，P = 0.011，AUC = 0.66]。按人乳头状瘤病毒状态、临床分期、年龄、性别、吸烟状况和级别进行分层分析保留统计学意义。与候选CpG位点（AJAP 1、SHANK 2、FOXA 2、MT 1A、ZNF 570、HOXC 4和HOXB 4）对应的基因表达也与患者的生存率显著相关。DNA甲基化、基因表达和临床信息的特征整合显示出上级的预后预测能力（AUC = 0.78）。结合DNA甲基化、基因表达和临床信息的预后标志比仅结合临床信息的预后标志更有价值。本文的在线版本（doi：10.1186/s13148-017-0392-9）包含补充材料，可供授权用户使用。
DNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma. A multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well. The seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10−10, area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient’s survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78). Prognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only. The online version of this article (doi:10.1186/s13148-017-0392-9) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
Langevin, Scott M.;Butler, Rondi A.;Eliot, Melissa;Pawlita, Michael;Maccani, Jennifer Z. J.;McClean, Michael D.;Kelsey, Karl T.
通讯作者：
Kelsey, Karl T.
影响因子：
11.5
作者：
Gu, Jian;Berman, David;Wu, Xifeng
通讯作者：
Wu, Xifeng
影响因子：
5.2
作者：
Krishnan, Neeraja M.;Dhas, Kunal;Panda, Binay
通讯作者：
Panda, Binay
影响因子：
5.8
作者：
Aryee, Martin J.;Jaffe, Andrew E.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.
DOI：
10.1158/1940-6207.capr-14-0179
发表时间：
2015-11
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Foy JP;Pickering CR;Papadimitrakopoulou VA;Jelinek J;Lin SH;William WN Jr;Frederick MJ;Wang J;Lang W;Feng L;Zhang L;Kim ES;Fan YH;Hong WK;El-Naggar AK;Lee JJ;Myers JN;Issa JP;Lippman SM;Mao L;Saintigny P
通讯作者：
Saintigny P