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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 PolyMAX frequency domain method: a new standard for modal parameter estimation 显示文摘 | BART P HERMAN V D A PATRICK G | 2004 | Shock and Vibration2004，，11： | 1 |
| 3 | Mutational analysis of the catalytic centre of the Citrobacter freundii AmpD N - acetylmuramyl - L - alanine amidase 显示文摘 | Catherine G Dominique D Bart D | 2004 | Biochemical Society2004，377，11： | 1 |
| 4 | Regulatory role of SGTI in early R Gene-Mediated plant defenses显示文摘 | Mark J Paul M Katherine K Bart J Jonathan D G Jane E | 2002 | Science2002，295，15： | 1 |
| 5 | 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 |
| 6 | The PloyMAX frequency domain method:a new standard for modal parameter estimation显示文摘 | Bart P Herman V D A Patrick G | 2004 | Shock and Vibration2004，，11： | 1 |
| 7 | Echocardiographic quantification of myocardial function using tissue deformation imaging,a guide to image acquisition and analysis using tissue Doppler and speckle tracking显示文摘 | ARCO J T BART W L D B PAUL G M | 2007 | Cardiovasc Ultrasound2007，5，3： | 1 |
| 8 | Transoral Incisionless Fundoplication: 2-year Results from the Prospective Multicenter U.S. Study显示文摘 | Bell Reginald C W Barnes William E Carter Bart J Sewell Robert W Mavrelis Peter G Ihde Glenn M Hoddinott Kevin M Fox Mark A Freeman Katherine D Gunsberger Tanja Hausmann Mark G Dargis David Gill Brian DaCosta Wilson Erik Trad Karim S | 2014 | The American Surgeon2014，，11： | 1 |
| 9 | A review of pressure-driven membrane processes in wastewater treatment and drinking water production 显示文摘 | Bart V D B Carlo V Tim V G | 2003 | Environmental Progress2003，22，1： | 1 |
| 10 | 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 |
| 11 | 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 |
| 12 | Towards mapping library and information science显示文摘 | Janssens F Jacqueline L Wolfgang G Bart D M | 2006 | Information Processing & Management2006，42，6： | 1 |
| 13 | 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 |
| 14 | Continuous modeling of induced anisotropic damage in granite显示文摘 | Shao J F Hoxha D Bart M Homand F Duveau G Souley M Hoteit N | 1999 | International Journal of Rock Mechanics & Mining Sciences1999，36，： | 1 |
| 15 | An O2,cathode for rechargeable lithium batteries:The effect of a catalyst显示文摘 | D(E)BART A BAO J ARMSTRONG G | | 0，，02： | 1 |
| 16 | Extracellular matrix proteins differentially regu-late airway smooth muscle phenotype and function显示文摘 | BART G J D | 2007 | Am JPhysiol Lung Cell Mol Physiol2007，，292： | 1 |
| 17 | Automatic Inclusion of Middleware Performance Attributes into Architectural UML Software Models 显示文摘 | Tom V Bart D Frank G | 2005 | IEEE Trans Software Eng (S1077-2626)2005，31，8： | 1 |
| 18 | Automotive and Aerospace Applications of the PolyMAX Modal Parameter Estimation Method显示文摘 | Bart P Patrick G Herman V D A etc | 2004 | In Proceedings of IMAC 22 Dearborn M1 USA2004，2004，： | 1 |
| 19 | The PolyMAX frequency-domain method:a new standard for modal parameter estimation显示文摘 | Bart P Herman V D A Patrick G etc | 2004 | Shock and Vibration2004，，11： | 1 |
| 20 | Super absorbing polymers as an internal curing agent for mitigation of early-age cracking of highperformance concrete bridge decks显示文摘 | Bart C Matthew G Geert D S | 2011 | Construction and Building Materials2011，，25： | 1 |
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