Integrative Genome-Wide Gene Expression Profiling of Clear Cell Renal Cell Carcinoma in Czech Republic and in the United States

作者: Magdalena B. Wozniak , Florence Le Calvez-Kelm , Behnoush Abedi-Ardekani , Graham Byrnes , Geoffroy Durand

DOI: 10.1371/JOURNAL.PONE.0057886

关键词: BiologyGene expression profilingGeneticsGenomeDNA methylationClear cell renal cell carcinomaEpigeneticsCell activationGeneFold changeGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

摘要: Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal carcinoma (ccRCC) have been mostly performed in North American Western European populations, while the highest incidence rates are found Central/Eastern Europe. We conducted whole-genome profiling 101 pairs of ccRCC tumours adjacent non-tumour tissue from Czech patients recruited within "K2 Study", using Illumina HumanHT-12 v4 Expression BeadChips to explore molecular variations underlying biological clinical heterogeneity this cancer. Differential analysis identified 1650 significant probes (fold change ≥2 false discovery rate <0.05) mapping 630 up- 720 down-regulated unique genes. similar statistical RNA data 65 cases Cancer Genome Atlas (TCGA) project 60% (402) downregulated 74% (469) upregulated genes K2 series. The characterization significantly deregulated demonstrated involvement metabolic catabolic processes, excretion, oxidation reduction, ion transport response chemical stimulus, simultaneously were associated with immune inflammatory responses, hypoxia, stress, wounding, vasculature development activation. Furthermore, genome-wide DNA methylation 317 TCGA ccRCC/adjacent indicated that deregulation approximately 7% could be explained by epigenetic changes. Finally, survival 89 464 8 differential prognostic outcomes. In conclusion, a large proportion characteristics common two populations several may implications when validated further through cohorts.

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