Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.
Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.
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DOI：
10.1186/s13148-020-00998-z
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发表时间：
2021-01-18
影响因子：
5.7
通讯作者：
Robertson KD
中科院分区：
文献类型：
--
作者：
El Khoury LY;Fu S;Hlady RA;Wagner RT;Wang L;Eckel-Passow JE;Castle EP;Stanton ML;Thompson RH;Parker AS;Ho TH;Robertson KD
尽管使用预后算法和标准监测指南，但最初诊断为低风险透明细胞肾细胞癌（ccRCC）的患者中有17%最终复发并死于复发性疾病，这表明需要额外的分子参数来改善预后。 为了解决低风险人群中ccRCC分类的差距，我们对甲基化特征进行了全基因组分析，该分析能够区分通过马约临床分期、大小、等级和坏死评分（SSIGN 0-3）分类为“低风险”的亚组内的复发性和非复发性ccRCC。这种方法揭示了复发患者具有全局高甲基化肿瘤，并且在5929个CpG上甲基化显著不同。差异甲基化CpG（DMCpGs）富集在调节细胞生长和侵袭的调控区域和基因中。一个DMCpG亚组在独立数据集中将低SSGN组分层为高和低复发风险，表明DNA甲基化增强了SSGN评分的预后能力。这项研究报告了复发性ccRCC患者肿瘤中的整体DNA超甲基化。此外，除了SSIGN评分外，DMCpG还能够区分侵袭性和侵袭性较低的肿瘤。因此，DNA甲基化本身是一种潜在的强生物标志物，可进一步改善低风险SSGN评分（0-3）患者的预后能力。
Despite using prognostic algorithms and standard surveillance guidelines, 17% of patients initially diagnosed with low risk clear cell renal cell carcinoma (ccRCC) ultimately relapse and die of recurrent disease, indicating additional molecular parameters are needed for improved prognosis. To address the gap in ccRCC prognostication in the lower risk population, we performed a genome-wide analysis for methylation signatures capable of distinguishing recurrent and non-recurrent ccRCCs within the subgroup classified as ‘low risk’ by the Mayo Clinic Stage, Size, Grade, and Necrosis score (SSIGN 0–3). This approach revealed that recurrent patients have globally hypermethylated tumors and differ in methylation significantly at 5929 CpGs. Differentially methylated CpGs (DMCpGs) were enriched in regulatory regions and genes modulating cell growth and invasion. A subset of DMCpGs stratified low SSIGN groups into high and low risk of recurrence in independent data sets, indicating that DNA methylation enhances the prognostic power of the SSIGN score. This study reports a global DNA hypermethylation in tumors of recurrent ccRCC patients. Furthermore, DMCpGs were capable of discriminating between aggressive and less aggressive tumors, in addition to SSIGN score. Therefore, DNA methylation presents itself as a potentially strong biomarker to further improve prognostic power in patients with low risk SSIGN score (0–3).
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影响因子：
3.8
作者：
Evelonn, Emma Andersson;Landfors, Mattias;Degerman, Sofie
通讯作者：
Degerman, Sofie
DOI：
10.1038/nrurol.2010.47
发表时间：
2010-05
期刊：
Nature reviews. Urology
影响因子：
--
作者：
通讯作者：
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影响因子：
4
作者：
Lasseigne BN;Brooks JD
通讯作者：
Brooks JD
通过BAP1和PBRM1表达鉴定的透明细胞肾细胞癌亚型。
DOI：
10.1016/j.juro.2015.07.113
发表时间：
2016-01
期刊：
The Journal of urology
影响因子：
--
作者：
Joseph RW;Kapur P;Serie DJ;Parasramka M;Ho TH;Cheville JC;Frenkel E;Parker AS;Brugarolas J
通讯作者：
Brugarolas J
DOI：
10.1158/1078-0432.ccr-12-3886
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hakimi AA;Ostrovnaya I;Reva B;Schultz N;Chen YB;Gonen M;Liu H;Takeda S;Voss MH;Tickoo SK;Reuter VE;Russo P;Cheng EH;Sander C;Motzer RJ;Hsieh JJ;ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators
通讯作者：
ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators