Genome-Wide Identification of a Methylation Gene Panel as a Prognostic Biomarker in Nasopharyngeal Carcinoma
Genome-Wide Identification of a Methylation Gene Panel as a Prognostic Biomarker in Nasopharyngeal Carcinoma
复制标题
全基因组鉴定甲基化基因组作为鼻咽癌的预后生物标志物
DOI：
10.1158/1535-7163.mct-15-0260
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发表时间：
2015-12-01
影响因子：
5.7
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Jiang, Wei;Liu, Na;Ma, Jun
DNA甲基化是最著名的表观遗传标记，可用作许多癌症的预后生物标志物。我们研究了鼻咽癌（NPC）患者的DNA甲基化状态和生存率。应用Illumina 450 K微珠芯片检测了24例鼻咽癌组织和24例非癌鼻咽炎活检组织（NCNBT）中的异常DNA甲基化基因。采用亚硫酸氢盐焦磷酸测序法对454例鼻咽癌患者的DNA甲基化与临床预后的相关性进行了评估。全基因组甲基化分析表明，鼻咽癌组织中有不同的DNA甲基化模式与NCNBT相比。在所有显著的CpG位点中，鉴定出β变化>= 0.2的2,173个CpG位点（1,880个高甲基化，293个低甲基化）（P < 0.05）。用平均Z-评分法构建了包含6个高甲基化基因的甲基化基因组。与低甲基化患者相比，高甲基化训练队列患者的无病生存期[DFS，HR，2.26; 95%置信区间（CI），1.28-4.01; P，0.005]和总生存期（OS，HR，2.47; 95% CI，1.30-4.71; P，0.006）较差。在验证中有相似的结果（DFS，HR，2.07; 95% CI，1.17-3.67; P，0.013; OS，HR，1.83; 95% CI，1.01-3.31; P，0.046）和独立队列（DFS，HR，1.94; 95% CI，1.08-3.47; P，0.026; OS，HR，2.09; 95% CI，1.10-3.98; P，0.022）。分析表明，甲基化基因组是一个独立的预后因素。此外，低甲基化患者对同步化疗有良好的反应，DFS（P = 0.045）和OS（P = 0.031）有所改善，而高甲基化患者没有从同步化疗中获益。六个高甲基化基因组与NPC患者的生存率低相关，表明其作为NPC管理临床医生的预后生物标志物的潜在有用性。（C）2015年AACR。
DNA methylation, the best known epigenetic marker, can be used as a prognostic biomarker in many cancers. We examined DNA methylation status and survival in nasopharyngeal carcinoma (NPC) patients. Aberrant DNA-methylated genes in 24 NPC tissues and 24 noncancer nasopharyngitis biopsy tissues (NCNBT) were identified using Illumina 450K BeadChip. Correlations between DNA methylation and clinical outcomes were evaluated using bisulfite pyrosequencing in 454 NPC patients. Genome-wide methylation analysis demonstrated that NPC tissues had distinct DNA methylation patterns compared with NCNBT. Among all significant CpG sites, 2,173 CpG sites with beta change >= 0.2 (1,880 hypermethylated, 293 hypomethylated) were identified (P < 0.05). A methylation gene panel comprising six hypermethylated genes was constructed with the average Z-score method. Patients in the training cohort with high methylation had poorer disease-free survival [DFS, HR, 2.26; 95% confidence interval (CI), 1.28-4.01; P, 0.005] and overall survival (OS, HR, 2.47; 95% CI, 1.30-4.71; P, 0.006) than those with low methylation. There were similar results in the validation (DFS, HR, 2.07; 95% CI, 1.17-3.67; P, 0.013; OS, HR, 1.83; 95% CI, 1.01-3.31; P, 0.046) and independent cohorts (DFS, HR, 1.94; 95% CI, 1.08-3.47; P, 0.026; OS, HR, 2.09; 95% CI, 1.10-3.98; P, 0.022). Analysis indicated that the methylation gene panel was an independent prognostic factor. Furthermore, patients with low methylation had a favorable response to concurrent chemotherapy with an improved DFS (P = 0.045) and OS (P = 0.031), whereas patients with high methylation did not benefit from concurrent chemotherapy. The six-hypermethylated gene panel was associated with poor survival in patients with NPC, demonstrating its potential usefulness as a prognostic biomarker to clinicians in NPC management. (C)2015 AACR.