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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 | An HIV-1 clade C DNA prime,NYVAC boost vaccine regimen induces reliable,polyfunctional,and long-lasting T cell responses显示文摘 | Harari A Bart PA St(o)hr W Tapia G Garcia M Medjitna-Rais E Burnet S Cellerai C Erlwein O Barber T Moog C Liljestrom P Wagner R Wolf H Kraehenbuhl JP Esteban M Heeney J Frachette MJ Tartaglia J McCormack S Babiker A Weber J Pantaleo G | 2008 | J Exp Med2008，205，1： | 1 |
| 3 | 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 |
| 4 | Competitive adsorption of nonionic surfactant and nonionic polymer on silica显示文摘 | Bart R P Frans A M L Luuk K K | 2007 | Langmuir2007，23，： | 1 |
| 5 | Biomarkers in upper Holocene Eastern North Sea and Wadden Sea sediments显示文摘 | BART E VD W IC R CATHARINA J M P | 2000 | Organic Geochemistry2000，31，： | 1 |
| 6 | 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 |
| 7 | Molecular cloning and nucleotide sequence of hog cholera envelope glycoprotein EI 显示文摘 | Moonmann R J M Warmendarm P A M Bart V M | 1990 | Virology1990，177，： | 1 |
| 8 | Competitive adsorption of nonionic surfactant and nonionic polymer on silica显示文摘 | BART R P FRANS A M L LUUK K K | 2007 | Langmuir2007，23，： | 1 |
| 9 | Reference-based stochastic subspace identification for output-only medal analysis 显示文摘 | Bart P Guido DE R | 1999 | Mechanical Systems and Signal Processing1999，13，6： | 1 |
| 10 | Analytical derivatiza- tion-a tool for determination of orotic acid显示文摘 | HUSKOVIt R BART/I_K P CP L | 2004 | Journal of Chro- matography B2004，799，2： | 1 |
| 11 | Two-dimensional non-isothermal model for toluene adsorption in a fixed-bed adsorber显示文摘 | Bart H J Germerdonk R Ning P | 1996 | Chemical Engineering and Processing1996，35，1： | 1 |
| 12 | 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 |
| 13 | Competitive adsorption of nonionic surfactant and nonionic polymer on silica显示文摘 | Bart R P Frans A M L Luuk K K | 2007 | Langmuir2007，23，： | 1 |
| 14 | Two-dimensional non-isothermal model for toluene adsorption in a fixed-bed adsorber 显示文摘 | Bart H J Germerdonk R Ning P | 1996 | Chemical Engineering and Processing1996，35，1： | 1 |
| 15 | 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 |
| 16 | Search for bound States of the η meson in light Nuclei显示文摘 | Chrien R E Bart S Pile P | 1988 | Phys Rev Lett1988，60，25： | 1 |
| 17 | Behavior evidence of trigeminal neuralgia neuropathic pain following chronic constriction injury to the rat's infraorbital nerve显示文摘 | BART P STRASSMAN A M MACIEWICZ R J | 1994 | The Journal of Neuroseience1994，14，5： | 1 |
| 18 | Expression of the stem cell marker ALDH1in BRCA1related breast cancer显示文摘 | Heerma van Voss M R van der Groep P Bart J | 2011 | Cellular Onc2011，34，1： | 1 |
| 19 | Neurological gait disorders in elderly people: clinical approach and classification显示文摘 | Anke H Snijders Bart P van de Warrenburg Nir Giladi Bastiaan R Bloem | 2006 | Lancet Neurology2006，，1： | 1 |
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