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| 1 | Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma显示文摘AIM To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS In silico DNA methylation analysis of 353 epigenetic clock Cp G sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer(CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated agerelated genes, secreted frizzled related protein 1(SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting(MS-HRM) analysis. m RNA expression of age-related 'epigenetic clock' genes was studied using Affymetrix HGU133 Plus2.0 whole transcriptome data of 153 colonic biopsy samples(49 healthy adult, 49 adenoma, 49 CRC, 6 healthy children)(GEO accession numbers: GSE37364, GSE10714, GSE4183, GSE37267). Whole promoter methylation analysis of genes showing inverse DNA methylationgene expression data was performed on 30 colonic samples using methyl capture sequencing.RESULTS Fifty-seven age-related Cp G sites including hypermethylated PPP1R16 B, SFRP1, SYNE1 and hypomethylated MGP, PIPOX were differentially methylated between CRC and normal tissues(P < 0.05, ?β≥ 10%). In the adenoma vs normal comparison, 70 CpG sites differed significantly, including hypermethylated DKK3, SDC2, SFRP1, SYNE1 and hypomethylated CEMIP, SPATA18(P < 0.05, ?β≥ 10%). In MS-HRM analysis, the SFRP1 promoter region was significantly hypermethylated in CRC(55.0% ± 8.4 %) and adenoma tissue samples(49.9% ± 18.1%) compared to normal adult(5.2% ± 2.7%) and young(2.2% ± 0.7%) colonic tissue(P < 0.0001). DNA methylation of SFRP1 promoter was slightly, but significantly increased in healthy adults compared to normal young samples(P < 0.02). This correlated with significantly increased SFRP1 m RNA levels in children compared to normal adult samples(P < 0.05). In CRC tissue the mR NA expression of 117 agerelated genes were changed, while in adenoma samples 102 genes showed differential expression compared with normal colonic tissue(P < 0.05, logF C > 0.5). The change of expression for several genes including SYNE1, CLEC3 B, LTBP3 and SFRP1, followed the same pattern in aging and carcinogenesis, though not for all genes(e.g., MGP). CONCLUSION Several age-related DNA methylation alterations can be observed during CRC development and progression affecting the m RNA expression of certain CRC- and adenoma-related key control genes. | Orsolya Galamb Alexandra Kalmár Barbara Kinga Barták árpád V Patai Katalin Leiszter Bálint Péterfia Barnabás Wichmann Gábor Valcz Gábor Veres Zsolt Tulassay Béla Molnár | 2016 | World Journal of Gastroenterology2016，22，47： | 7 |
| 2 | The effects of boundary conditions and initial out-of-roundness on the strength of thin-walled cylinders subject to external hydrostatic pressure显示文摘 | Galletly G D Bart R | 1956 | Journal of Applied Mechanics''1956，78，： | 1 |
| 3 | A new peroxotungsten heteropoly anion with special oxidizing properties:Synthesis and structure of tetrahexylammonium tetra(diperoxotungsto)phosphate(3-)显示文摘 | VENTURELLO C D' ALOISTO R BART J C J | 1985 | J Mole Cata1985，32，： | 1 |
| 4 | Stochastic System Identification for Operational Modal Analysis显示文摘 | Bart P Buido D R | 2001 | Journal of Dynamic Systems Measurement and Control2001，123，12： | 1 |
| 5 | lntracranial hemorrhage in herpes simplex encephalitis : an unusual presentation 显示文摘 | ERDEM G VANDERFORD P A BART R D | 2002 | Pediatr Neurol2002，27，3： | 1 |
| 6 | A New Perexotungsten Heterepoly Anion with Special Oxidizing Properties: Synthesis and Structure of TetrahexylammoniumTetra ( Diperoxotungsto ) Phosphate ( 3 - ) 显示文摘 | Venturello C AIoisio R D Bart J C | 1985 | Journal of Molecular Catalysis1985，32，1： | 1 |
| 7 | The role of leukocytes following cerebral ischemia: Pathogenic variable or bystander reaction to emerging infarct 显示文摘 | Emerich D F Dean R L Bartes R T | 2002 | Exp Neurol2002，173，： | 1 |
| 8 | Effects of boundary conditions and initial out-of-roundness on the strength of thin- walled cylinders subjected to external pressure 显示文摘 | Galletly G D Bart R | 1956 | Journal of Applied Mechanics-transactions of theASME1956，，3： | 1 |
| 9 | Effects of boundary conditions and initial out-of-roundness on the strength of thin-walled cylinders subject to external hydrostatic pressure显示文摘 | Galletly G D Bart R | 1956 | Journal of Applied Mechanics ASME1956，23，3： | 1 |
| 10 | No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the β-cleaved C-terminal APP fragment显示文摘 | Bart P F R Oliver W Wilma D J | 2003 | Neurobiology of Disease2003，12，： | 1 |
| 11 | N-thiolated β- lactams:Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus显示文摘 | Kevin D R Bart H Timothy E Long | 2007 | Bioorganic & Medicinal Chemistry2007，15，： | 1 |
| 12 | A new peroxotungsten heteropoly anion with special oxidizing properties:Synthesis and structure of tetrahexylammonium tetra (diperoxotungsto)phosphate(3-)显示文摘 | VENTURELLO C D' ALOISIO R BART C J | 1985 | J Mol Catal1985，32，： | 1 |
| 13 | A new peroxotungsten heterepoly anion with special oxidizing properties:synthesis and structure of tetrahexylammonium tetra (diperoxotungsto) phosphate ( 3 - ) 显示文摘 | Venturello C D'Aloisio R Bart J C J | 1985 | J Mol Cata11985，32，1： | 1 |
| 14 | Phylogeny of sucker mouth catfishes (Mochokidae: Chiloglanis) from Kenya: the utility of Growth Hormone introns in species level phylogenies显示文摘 | Schmidt R C Bart Jr H L Nyingi D W | 2014 | Molecular Phylogenetics and Evolution2014，79，： | 1 |
| 15 | 显示文摘 | Bart A J Noordover D Haveman R | 2011 | Journal of Applied Polymer Science2011，121，3： | 1 |
| 16 | One-year monitoring of the Z24-bridge:environmental effects versus damage events显示文摘 | Bart P Guido D R | 2001 | Earthquake Engineering and Structural Dynamics2001，30，： | 1 |
| 17 | Lung cancer and cyclooxygenase-2 显示文摘 | Castelao J E Bart R D 3rd Di Perna C A | 2003 | Ann Thorac Surg2003，76，： | 1 |
| 18 | Scan- nerless range imaging with a square wave 显示文摘 | Maritza R Muguira John T Sackos Bart D Bradley | 1995 | Proceedings of SPIE1995，24，： | 1 |
| 19 | Phylogeography of the greenside darter complex,Etheostoma blennioides (Teleostomi : Percidae) : A wide-ranging polytypic taxon显示文摘 | Piller K R Bart JR H L Hurley D L | 2008 | Mol Phylogenet Evol2008，46，： | 1 |
| 20 | Maximin Latin hypercube designs in two dimensions显示文摘 | EDWIN R D BART H | 2005 | Operations Research2005，55，1： | 1 |
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