A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes
A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes
复制标题
DOI：
10.1158/1541-7786.mcr-15-0395
复制
发表时间：
2016-09-01
影响因子：
5.2
通讯作者：
Panda, Binay
中科院分区：
文献类型：
--
作者：
Krishnan, Neeraja M.;Dhas, Kunal;Panda, Binay
口腔舌鳞状细胞癌（OTSCC）是一种同质的头颈部侵袭性肿瘤，早期扩散到淋巴结，并且具有较高的局部衰竭发生率。此外，年轻人群中口腔癌的发病率也在上升。研究与基因表达改变相关的功能性DNA甲基化变化对于理解肿瘤发生和转移的机制至关重要。这些研究也为OTSCC中与病毒感染、肿瘤转移和患者生存相关的生物标志物提供了重要的见解。因此，我们对肿瘤（N = 52）进行了全基因组甲基化分析，并将甲基化改变与差异基因表达联系起来。最小肿瘤特异性DNA 5-甲基胞嘧啶标记在16个不同的差异甲基化区域附近鉴定了基因，并使用来自癌症基因组图谱队列的基因组数据进行了验证。在我们的队列中，MIR10B的高甲基化与其靶基因NR4A3和BCL2L11的差异表达显著相关（P = 0.0125和P = 0.014），与患者的无病生存率呈负相关（P = 9E - 15和P = 2E - 15）。最后，发现FUT3、TRIM5、TSPAN7、MAP3K8、RPS6KA2、SLC9A9和NPAS3基因的差异甲基化可预测某些临床和流行病学参数。(c) 2016年aacr。
Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of aggressive tumors in the head and neck region that spread early to lymph nodes and have a higher incidence of regional failure. In addition, there is a rising incidence of oral tongue cancer in younger populations. Studies on functional DNA methylation changes linked with altered gene expression are critical for understanding the mechanisms underlying tumor development and metastasis. Such studies also provide important insight into biomarkers linked with viral infection, tumor metastasis, and patient survival in OTSCC. Therefore, we performed genome-wide methylation analysis of tumors (N = 52) and correlated altered methylation with differential gene expression. The minimal tumor-specific DNA 5-methylcytosine signature identified genes near 16 different differentially methylated regions, which were validated using genomic data from The Cancer Genome Atlas cohort. In our cohort, hypermethylation of MIR10B was significantly associated with the differential expression of its target genes NR4A3 and BCL2L11 (P = 0.0125 and P = 0.014, respectively), which was inversely correlated with disease-free survival (P = 9E - 15 and P = 2E - 15, respectively) in patients. Finally, differential methylation in FUT3, TRIM5, TSPAN7, MAP3K8, RPS6KA2, SLC9A9, and NPAS3 genes was found to be predictive of certain clinical and epidemiologic parameters. (C) 2016 AACR.