Vlaanderen Jelle, Leenders Max, Chadeau-Hyam Marc, Portengen Lützen, Kyrtopoulos Soterios A, Bergdahl Ingvar A, Johansson Ann-Sofie, Hebels Dennie D G A J, de Kok Theo M C M, Vineis Paolo, Vermeulen Roel C H
Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
BMC Genomics. 2017 Mar 20;18(1):239. doi: 10.1186/s12864-017-3627-4.
We recently identified 700 genes whose expression levels were predictive of chronic lymphocytic leukemia (CLL) in a genome-wide gene expression analysis of prediagnostic blood from future cases and matched controls. We hypothesized that a large fraction of these markers were likely related to early disease manifestations. Here we aim to gain a better understanding of the natural history of the identified markers by comparing results from our prediagnostic analysis, the only prediagnostic analysis to date, to results obtained from a meta-analysis of a series of publically available transcriptomics profiles obtained in incident CLL cases and controls.
We observed considerable overlap between the results from our prediagnostic study and the clinical CLL signals (p-value for overlap Bonferroni significant markers 0.01; p-value for overlap nominal significant markers < 2.20e-16). We observed similar patterns with time to diagnosis and similar functional annotations for the markers that were identified in both settings compared to the markers that were only identified in the prediagnostic study. These results suggest that both gene sets operate in similar pathways.
An overlap exists between expression levels of genes predictive of CLL identified in prediagnostic blood and expression levels of genes associated to CLL at the clinical stage. Our analysis provides insight in a set of genes for which expression levels can be used to follow the time-course of the disease; providing an opportunity to study CLL progression in more detail in future studies.
我们最近在一项针对未来慢性淋巴细胞白血病（CLL）病例的诊断前血液与匹配对照的全基因组基因表达分析中，鉴定出700个基因，其表达水平可预测CLL。我们推测这些标志物中的很大一部分可能与疾病早期表现有关。在此，我们旨在通过将我们的诊断前分析结果（这是迄今为止唯一的诊断前分析）与对一系列在初发CLL病例和对照中获得的公开可用转录组学图谱进行荟萃分析所得到的结果进行比较，从而更好地了解已鉴定标志物的自然史。
我们观察到诊断前研究结果与临床CLL信号之间存在相当大的重叠（重叠的Bonferroni显著标志物的p值为0.01；重叠的名义显著标志物的p值<2.20e - 16）。与仅在诊断前研究中鉴定出的标志物相比，我们观察到在两种情况下鉴定出的标志物在诊断时间方面具有相似模式，并且具有相似的功能注释。这些结果表明这两组基因在相似的途径中发挥作用。
在诊断前血液中鉴定出的预测CLL的基因表达水平与临床阶段与CLL相关的基因表达水平之间存在重叠。我们的分析为一组基因提供了见解，其表达水平可用于跟踪疾病的时间进程；为未来研究更详细地研究CLL进展提供了机会。
