191 research outputs found
Genome-wide profiling of methylation identifies novel targets with aberrant hyper-methylation and reduced expression in low-risk myelodysplastic syndromes
Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases. © 2013 Macmillan Publishers Limited All rights reserved
ColoLipidGene: Signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients
Lipid metabolism plays an essential role in carcinogenesis due to the requirements
of tumoral cells to sustain increased structural, energetic and biosynthetic precursor
demands for cell proliferation. We investigated the association between expression
of lipid metabolism-related genes and clinical outcome in intermediate-stage colon
cancer patients with the aim of identifying a metabolic profile associated with greater
malignancy and increased risk of relapse. Expression profile of 70 lipid metabolismrelated
genes was determined in 77 patients with stage II colon cancer. Cox regression
analyses using c-index methodology was applied to identify a metabolic-related
signature associated to prognosis. The metabolic signature was further confirmed in
two independent validation sets of 120 patients and additionally, in a group of 264
patients from a public database. The combined analysis of these 4 genes, ABCA1,
ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to
accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with
strong statistical power in the four independent groups of patients. The identification
of a group of 4 genes that predict survival in intermediate-stage colon cancer patients
allows delineation of a high-risk group that may benefit from adjuvant therapy, and
avoids the toxic and unnecessary chemotherapy in patients classified as low-risk groupThis work was supported by Ministerio de Ciencia e
Innovación del Gobierno de España (Plan Nacional I + D +
i AGL2013–48943-C2–2-R and IPT-2011–1248-060000),
Comunidad de Madrid (P2013/ABI-2728. ALIBIRDCM)
and European Union Structural Funds. CIBEREHD
is funded by the Instituto de Salud Carlos III. This is a
collaborative study between the Molecular Oncology Unit
of The Institute of Advanced Studies of Madrid IMDEA Food
and the Grupo Español Multidisciplinar en Cáncer
Digestivo (GEMCAD
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