Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.
Integrative genome-wide gene expression profiling of clear cell renal cell carcinoma in Czech Republic and in the United States.
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DOI：
10.1371/journal.pone.0057886
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Scelo G
中科院分区：
文献类型：
--
作者：
Wozniak MB;Le Calvez-Kelm F;Abedi-Ardekani B;Byrnes G;Durand G;Carreira C;Michelon J;Janout V;Holcatova I;Foretova L;Brisuda A;Lesueur F;McKay J;Brennan P;Scelo G
针对传统透明细胞肾细胞癌 (ccRCC) 的基因表达微阵列和下一代测序工作主要在北美和西欧人群中进行，而中欧/东欧的发病率最高。我们使用 Illumina HumanHT-12 v4 Expression BeadChips 对“K2 研究”中招募的捷克患者的 101 对 ccRCC 肿瘤和邻近非肿瘤肾组织进行了全基因组表达谱分析，以探索这种癌症的生物学和临床异质性背后的分子变异。差异表达分析鉴定出 1650 个显着探针（倍数变化≥2，错误发现率 <0.05），映射到 630 个上调和 720 个下调的独特基因。我们对来自癌症基因组图谱 (TCGA) 项目的 65 例 ccRCC 病例的 RNA 测序数据进行了类似的统计分析，并确定了 K2 系列中发现的 60% (402) 下调基因和 74% (469) 上调基因。显着失调的基因的生物学特征表明，下调的基因参与代谢和分解代谢过程、排泄、氧化还原、离子运输和对化学刺激的反应，而同时上调的基因与免疫和炎症反应、对缺氧、应激、受伤、脉管系统发育和细胞激活的反应有关。此外，对 317 个 TCGA ccRCC/邻近非肿瘤肾组织对的全基因组 DNA 甲基化分析表明，约 7% 的基因失调可以通过表观遗传变化来解释。最后，对 89 个 K2 和 464 个 TCGA 病例进行生存分析，确定了与不同预后结果相关的 8 个基因。总之，大部分 ccRCC 分子特征对于两个人群来说是共同的，并且通过大型临床队列进一步验证时，其中一些可能具有临床意义。
Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the “K2 Study”, using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05) mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA) project and identified 60% (402) of the downregulated and 74% (469) of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.
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影响因子：
3.3
作者：
Davidson, Ben;Stavnes, Helene Tuft;Wang, Tian-Li
通讯作者：
Wang, Tian-Li
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
7
作者：
Boer, JM;Huber, WK;Poustka, A
通讯作者：
Poustka, A
透明细胞肾细胞癌基因表达的荟萃分析定义了一种变异子组，并鉴定了性别对肿瘤生物学的影响。
影响因子：
23.4
作者：
Brannon, A. Rose;Haake, Scott M.;Hacker, Kathryn E.;Pruthi, Raj S.;Wallen, Eric M.;Nielsen, Matthew E.;Rathmell, W. Kimryn
通讯作者：
Rathmell, W. Kimryn
符号：一种并行的，开源的，可自由使用的基于网络选择的工具，用于基因选择和生存和审查数据的分子特征。
影响因子：
3
作者：
Diaz-Uriarte, Ramon
通讯作者：
Diaz-Uriarte, Ramon