Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis.
Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis.
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DOI：
10.1186/s13059-018-1511-4
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发表时间：
2018-09-25
期刊：
影响因子：
12.3
通讯作者：
Waldron L
中科院分区：
文献类型：
--
作者：
Ma S;Ogino S;Parsana P;Nishihara R;Qian Z;Shen J;Mima K;Masugi Y;Cao Y;Nowak JA;Shima K;Hoshida Y;Giovannucci EL;Gala MK;Chan AT;Fuchs CS;Parmigiani G;Huttenhower C;Waldron L
以前根据转录本确定结直肠癌和其他癌症亚型的方法都假定存在离散的亚型。我们分析了来自大量患者的结直肠肿瘤的基因表达模式，以验证这一假设，并提出了一种方法，以确定存在于独立研究和队列中的潜在的亚型连续体。我们通过整合18个已发表的基因表达数据集和3700名 患者来检验离散的结直肠癌亚型的假设，与以前的报道相反，我们没有发现支持离散转录亚型存在的证据。使用荟萃分析方法来识别存在于多个数据集中的共表达模式，我们识别并定义稳健的、连续变化的亚型分数来代表CRC转录本。亚型得分与已建立的亚型一致(包括微卫星不稳定性和先前提出的离散转录组亚型)，但比离散亚型更能代表整体转录活性。与不连续的亚型相比，评分对肿瘤的位置、分期、分级和无病生存时间的预测也更好。基因集浓缩分析显示，亚型分数表征了T细胞功能、炎症反应和细胞周期蛋白依赖性激酶对DNA复制的调节。我们发现没有证据支持CRC转录组的离散亚型，相反，我们提出了两个有效的分数来更好地表征CRC转录组的连续性。本文的在线版本(10.1186/s13059-0181511-4)包含补充材料，可供授权用户使用。
Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose an approach to identify potentially a continuum of subtypes that are present across independent studies and cohorts. We examine the assumption of discrete CRC subtypes by integrating 18 published gene expression datasets and > 3700 patients, and contrary to previous reports, find no evidence to support the existence of discrete transcriptional subtypes. Using a meta-analysis approach to identify co-expression patterns present in multiple datasets, we identify and define robust, continuously varying subtype scores to represent CRC transcriptomes. The subtype scores are consistent with established subtypes (including microsatellite instability and previously proposed discrete transcriptome subtypes), but better represent overall transcriptional activity than do discrete subtypes. The scores are also better predictors of tumor location, stage, grade, and times of disease-free survival than discrete subtypes. Gene set enrichment analysis reveals that the subtype scores characterize T-cell function, inflammation response, and cyclin-dependent kinase regulation of DNA replication. We find no evidence to support discrete subtypes of the CRC transcriptome and instead propose two validated scores to better characterize a continuity of CRC transcriptomes. The online version of this article (10.1186/s13059-018-1511-4) contains supplementary material, which is available to authorized users.
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整合染色体畸变和基因表达谱以剖析直肠肿瘤发生。
影响因子：
3.8
作者：
Lips, Esther H.;van Eijk, Ronald;de Graaf, Eelco J. R.;Oosting, Jan;de Miranda, Noel F. C. C.;Karsten, Tom;de Velde, Cornelis J. van;Eilers, Paul H. C.;Tollenaar, Rob A. E. M.;van Wezel, Tom;Morreau, Hans
通讯作者：
Morreau, Hans
影响因子：
2.9
作者：
Lili LN;Matyunina LV;Walker LD;Daneker GW;McDonald JF
通讯作者：
McDonald JF
影响因子：
12.4
作者：
Linnekamp, Janneke F.;van Hooff, Sander R.;Medema, Jan Paul
通讯作者：
Medema, Jan Paul
影响因子：
2
作者：
Heinze, G;Schemper, M
通讯作者：
Schemper, M
影响因子：
16.6
作者：
Isella C;Brundu F;Bellomo SE;Galimi F;Zanella E;Porporato R;Petti C;Fiori A;Orzan F;Senetta R;Boccaccio C;Ficarra E;Marchionni L;Trusolino L;Medico E;Bertotti A
通讯作者：
Bertotti A