Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.
Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.
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DOI：
10.1186/s40364-021-00349-x
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发表时间：
2021-12-20
影响因子：
11.1
通讯作者：
Aouizerat BE
中科院分区：
文献类型：
--
作者：
Viet CT;Zhang X;Xu K;Yu G;Asam K;Thomas CM;Callahan NF;Doan C;Walker PC;Nguyen K;Kidd SC;Lee SC;Grandhi A;Allen CT;Young S;Melville JC;Shum JW;Viet DT;Herford AS;Roden DF;Gonzalez ML;Zhong JF;Aouizerat BE
口腔鳞状细胞癌(OSCC)的生存率很低。迫切需要开发更精确的风险评估方法，以适应临床治疗。口腔鳞状细胞癌的表观基因组相关性研究尚未产生一个可行的生物标记物。这些研究依赖于甲基化阵列平台，这些平台对甲基组的分析能力有限。在这项研究中，我们使用一种全面的甲基化定量技术-甲基化序列(MC-Seq)和刷拭子样本来开发一种非侵入性的、易于翻译的方法来描述口腔鳞癌患者的甲基组。3例口腔鳞状细胞癌患者接受了癌组织和对侧正常组织的收集以及刷检，每个患者总共4个样本。使用SureSelectXT甲基序列平台进行表观基因组范围的DNA甲基化定量。比较刷检和组织标本的DNA质量和甲基化位点分辨率。确定了每个患者和部位(即癌症或正常)的刷拭子与组织的相关性和甲基化值差异。计算癌症和正常组织之间的相关性，以及每个患者的刷检样本，以确定在临床生物标记物研究中使用刷检的DNA甲基化标记的稳健性。组织和刷拭子样本之间的DNA产量没有显著差异。所有样本的作图效率都超过90%，组织和刷子拭子之间没有差异。覆盖深度至少10倍的CpG站点的平均数量刷子拭子为2,716,674个，组织为2,903,261个。匹配的组织和毛刷拭子具有良好的相关性(癌样本的r = 为0.913，正常样本的r = 为0.951)。前1000个Cpg在癌组织和正常组织中的甲基化状态有显著差异(平均p值 = 为0.00021)，而在组织和刷检之间无显著差异(平均p值 = 为0.11)。我们的结果表明，MC-Seq是癌症生物标记物研究中表观基因组图谱的有效平台，与基于阵列的平台相比，具有更广泛的甲基组覆盖范围。刷拭子活检为MC-Seq提供了足够的DNA产量，综合起来，我们的发现为开发一种具有高翻译潜力的口腔癌非侵入性甲基组定量技术奠定了基础。网上版载有补充材料，可在10.1186/s40364-021-00349-x查阅。
Oral squamous cell carcinoma (OSCC) has poor survival rates. There is a pressing need to develop more precise risk assessment methods to tailor clinical treatment. Epigenome-wide association studies in OSCC have not produced a viable biomarker. These studies have relied on methylation array platforms, which are limited in their ability to profile the methylome. In this study, we use MethylCap-Seq (MC-Seq), a comprehensive methylation quantification technique, and brush swab samples, to develop a noninvasive, readily translatable approach to profile the methylome in OSCC patients. Three OSCC patients underwent collection of cancer and contralateral normal tissue and brush swab biopsies, totaling 4 samples for each patient. Epigenome-wide DNA methylation quantification was performed using the SureSelectXT Methyl-Seq platform. DNA quality and methylation site resolution were compared between brush swab and tissue samples. Correlation and methylation value difference were determined for brush swabs vs. tissues for each respective patient and site (i.e., cancer or normal). Correlations were calculated between cancer and normal tissues and brush swab samples for each patient to determine the robustness of DNA methylation marks using brush swabs in clinical biomarker studies. There were no significant differences in DNA yield between tissue and brush swab samples. Mapping efficiency exceeded 90% across all samples, with no differences between tissue and brush swabs. The average number of CpG sites with at least 10x depth of coverage was 2,716,674 for brush swabs and 2,903,261 for tissues. Matched tissue and brush swabs had excellent correlation (r = 0.913 for cancer samples and r = 0.951 for normal samples). The methylation profile of the top 1000 CpGs was significantly different between cancer and normal samples (mean p-value = 0.00021) but not different between tissues and brush swabs (mean p-value = 0.11). Our results demonstrate that MC-Seq is an efficient platform for epigenome profiling in cancer biomarker studies, with broader methylome coverage than array-based platforms. Brush swab biopsy provides adequate DNA yield for MC-Seq, and taken together, our findings set the stage for development of a non-invasive methylome quantification technique for oral cancer with high translational potential. The online version contains supplementary material available at 10.1186/s40364-021-00349-x.
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影响因子：
3.7
作者：
Teh AL;Pan H;Lin X;Lim YI;Patro CP;Cheong CY;Gong M;MacIsaac JL;Kwoh CK;Meaney MJ;Kobor MS;Chong YS;Gluckman PD;Holbrook JD;Karnani N
通讯作者：
Karnani N
口腔癌中p16，rarbeta，e-钙粘蛋白，细胞周期蛋白A1和细胞神经蛋白的启动子甲基化：使用焦磷酸测序进行定量评估。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
4.6
作者：
Kim, Yi-Jun;Kim, Jin Ho
通讯作者：
Kim, Jin Ho
影响因子：
4.8
作者：
Tota, Joseph E.;Anderson, William F.;Chaturvedi, Anil K.
通讯作者：
Chaturvedi, Anil K.
影响因子：
3.8
作者：
Viet, Chi T.;Schmidt, Brian L.
通讯作者：
Schmidt, Brian L.