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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 | A case of se- vere Ebola virus infection complicated by gram-negative sep- ticemia显示文摘 | Kreuels B Wichmann D Emmerich P | 2014 | N Engl J Med2014，371，25： | 1 |
| 3 | Risk of Liver Decompensation Among HIV/Hepatitis C Virus–Coinfected Individuals With Advanced Fibrosis: Implications for the Timing of Therapy显示文摘 | Juan Macías Manuel Márquez Francisco Téllez Dolores Merino Patricia Jiménez-Aguilar Luis F. López-Cortés Enrique Ortega Miguel A. von Wichmann Antonio Rivero María Mancebo Jesús Santos Montserrat Pérez-Pérez Ignacio Suárez-Lozano Alberto Romero-Palacios A | 2013 | Clinical Infectious Diseases2013，，10： | 1 |
| 4 | Evaluation of clinical safety and beneficial effects of a fish oil contai- ning lipid emulsion ( Lipoplus, MLF541 ) : data from a prospective, randomized, muhicenter trial 显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，3： | 1 |
| 5 | On the economics of Internet peering显示文摘 | Wichmann T | 1998 | Netnomics1998，，2： | 1 |
| 6 | Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups显示文摘 | Scherag A Dina C Hinney A Vatin V Scherag S Vogel C I Muller T D Grallert H Wichmann H E Balkau B Heude B Jarvelin M R Hartikainen A L Levy-Marchal C Weill J Delplanque J Korner A Kiess W Kovacs P Rayner N W Prokopenko I McCarthy M I Schafer H Jarick I Bo | | 0，，04： | 1 |
| 7 | Correction of myopia by implantation of a concave Worst-iris claw lens into phakic eyes显示文摘 | Strobel J Wichmann W | 1991 | Refract Corneal Surg1991，7，： | 1 |
| 8 | Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion( Li- poplus, MLF541 ) : Data from a prospective, randomized, multicenter trial 显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，3： | 1 |
| 9 | Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion(Lipoplus, MLF541 ):date from a prospective, randomized, mulficenter trial 显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，： | 1 |
| 10 | Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion ( Lipoplus, MLF541 ) : Data from a prospective, randomized, muhicenter trial显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，3： | 1 |
| 11 | Evaluation of clinical safety and beneficial effects of a fish oil containing lipid emulsion ( Lipoplus, MLF541 ) : data from a prospective, randomized, multicenter trial 显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，： | 1 |
| 12 | Oscillations in the basal ganglia under normal conditions and in movement disorders]显示文摘 | Gatev P Darbin O Wichmann T | 2006 | Mov Disord2006，21，10： | 1 |
| 13 | Variation of particulate number and mass concentration in various size ranges of ambient aerosols in Eastern Germany 显示文摘 | Tueh T Brand P Wichmann H E | 1997 | Atmospheric Environment1997，，31： | 1 |
| 14 | Health effects during a smog episode in West Germany in 1985显示文摘 | Wichmann HE Mueller W Allhoff P | 1989 | Environ Health Perspect1989，79，： | 1 |
| 15 | A case of severe Ebola virus infection complicated by gram-negative septicemia显示文摘 | Kreuels B Wichmann D Emmerich P | 2014 | N Engl J Med2014，371，25： | 1 |
| 16 | Long-term neuro- muscular status in overdenture and complete denture pa- tients with severe mandibular atrophy 显示文摘 | Spitzl C Pr?schel P Wichmann M | 2012 | Int J Oral Maxillo- fac Implants2012，27，1： | 1 |
| 17 | Evaluation of clini-cal safety and beneficial effects of a fish oil containing lipid emul-sion(Lipoplus,MLF541):Data from a prospective,randomized,multicenter trial显示文摘 | Wichmann MW Thul P Czarnetzki HD | 2007 | Crit Care Med2007，35，3： | 1 |
| 18 | A case of severe Ebola virus infection complicated by gram- negative septicemia显示文摘 | Kreuels B Wichmann D Emmerich P Schmidt-Chanasit J de Heer G Kluge S | 2014 | N Engl J Med2014，371，： | 1 |
| 19 | Immunological effects of laparoscopic vs open colorectal surgery: A prospective clinilal study显示文摘 | Wichmann M W Huttl T P Winter H | 2005 | Arch Surg2005，140，7： | 1 |
| 20 | Variation of particle number and mass concentration in various size ranges of ambient aerosols in eastern Germany 显示文摘 | TUCH TH BRAND P WICHMANN H E | 1997 | Atmospheric Environment1997，31，24： | 1 |
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