Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma.
Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma.
复制标题
肺腺癌中候选表观遗传生物标志物的鉴定和验证。
DOI：
10.1038/srep35807
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发表时间：
2016-10-26
影响因子：
4.6
通讯作者：
Hansen LL
中科院分区：
文献类型：
--
作者：
Daugaard I;Dominguez D;Kjeldsen TE;Kristensen LS;Hager H;Wojdacz TK;Hansen LL
肺癌是全球癌症相关死亡的首要原因。DNA甲基化是一种调控基因表达的表观遗传机制，疾病特异性的甲基化变化可作为生物标志物。我们使用DNA甲基化微阵列比较了4例肺腺癌（LAC）患者的肿瘤组织和肿瘤相邻正常肺组织的全基因组甲基化模式，并确定了74个差异甲基化区域（DMRs）。通过甲基化敏感高分辨率熔解（MS - HRM）分析，在一个队列中选择了18个DMRs进行验证，该队列包括52例LAC患者的原发肿瘤和32例患者的肿瘤相邻正常肺组织。与以下基因和基因组区域相关的15个DMRs的甲基化显著增加得到了证实：OSR1、SIM1、GHSR、OTX2、LOC648987、HIST1H3E、HIST1H3G/HIST1H2BI、HIST1H2AJ/HIST1H2BM、HOXD10、HOXD3、HOXB3/HOXB4、HOXA3、HOXA5、Chr1(q21.1).A和Chr6(p22.1)。特别是OSR1、SIM1和HOXB3/HOXB4区域在LAC中显示出作为生物标志物的高潜力。对于OSR1，在47/48例LAC病例中检测到高甲基化，而在肿瘤相邻正常肺样本中仅为1/31。同样，与肿瘤相邻正常肺样本中的3/31和0/31相比，分别有45/49和36/48例LAC病例显示SIM1和HOXB3/HOXB4区域高甲基化。总之，本研究确定并验证了15个可作为LAC生物标志物的DMRs。
Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3, HOXA5, Chr1(q21.1).A, and Chr6(p22.1). In particular the OSR1, SIM1 and HOXB3/HOXB4 regions demonstrated high potential as biomarkers in LAC. For OSR1, hypermethylation was detected in 47/48 LAC cases compared to 1/31 tumor-adjacent normal lung samples. Similarly, 45/49 and 36/48 LAC cases compared to 3/31 and 0/31 tumor-adjacent normal lung samples showed hypermethylation of the SIM1 and HOXB3/HOXB4 regions, respectively. In conclusion, this study has identified and validated 15 DMRs that can be targeted as biomarkers in LAC.
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影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
--
作者：
Rauch, Tibor A.;Wang, Zunde;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
DOI：
10.1073/pnas.0710735105
发表时间：
2008-01-08
影响因子：
11.1
作者：
Rauch, Tibor A.;Zhong, Xueyan;Pfeifer, Gerd P.
通讯作者：
Pfeifer, Gerd P.
DOI：
10.6004/jnccn.2013.0084
发表时间：
2013-06-01
影响因子：
13.4
作者：
Ettinger, David S.;Akerley, Wallace;Hughes, Miranda
通讯作者：
Hughes, Miranda
影响因子：
8
作者：
Dammann, R;Takahashi, T;Pfeifer, GP
通讯作者：
Pfeifer, GP