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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 | Females in proestrus state maintain splenic immune functions and tolerate sepsis better than males显示文摘 | Zell Weger R Wichmann M W Ayala A | 1997 | Crit Care Med1997，25，： | 1 |
| 3 | Oral citrus seed extract显示文摘 | IONESCU G KIEHL R WICHMANN K F | 1991 | Journal of Orthomolecular Medicine1991，5，： | 1 |
| 4 | Chaudry IH:mechanism of immune suppression in males following trauma-hemorrhage:critical role of testosterone显示文摘 | Wichmann M Zellweger R De Maso C M | 1996 | Arch Surg1996，131，： | 1 |
| 5 | Enhanced immune responses in females as opposed to decreased responses in males following hemorrhagic shock 显示文摘 | Wichmann M W Zellweger R DeMaso C M | 1996 | Cytokine1996，8，： | 1 |
| 6 | Effect of surface treatment on the shear bond strength of three resin cements to a machinable feldspathic ceramic显示文摘 | Reich SM Wichmann M Frankenberger R | 2005 | J Biomed Mater Res B Appl Biomater2005，74，2： | 1 |
| 7 | Video head im-pulse test or caloric irrigation- Contemporary diagnostic tests{or vestibular scKwannoma显示文摘 | Blodow A Helbig R Wichmann N | 2013 | HN〇2013，61，781： | 1 |
| 8 | Functional and pathophysiological models of the basal ganglia 显示文摘 | Wichmann T De Long M R | 1996 | Current Opinion Neurobiology (S0959-4388)1996，6，6： | 1 |
| 9 | Fast-track rehabilitation in elective colorectal surgery patients: a prospective clinical and immunological single-centre study显示文摘 | Wichmann MW Eben R Angele MK | 2007 | ANZ J Surg2007，77，7： | 1 |
| 10 | Structural properties and applications of muhidentate aminobisphenolate metal complexes显示文摘 | Wichmann O Sillanpaa R Lehtonen A | 2012 | Coord Chem Rev2012，256，： | 1 |
| 11 | Functional and pathophysiological models of the basal ganglia显示文摘 | WICHMANN T DELONG M R | 1996 | CurrOpin Nearobiol1996，6，6： | 1 |
| 12 | 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 |
| 13 | Fast-track rehabilitation in elective colorectal surgery patients:a prospective clinical and immunological single-centure study显示文摘 | WICHMANN M W EBEN R ANGELE M K | 2007 | ANZ J Surg2007，77，7： | 1 |
| 14 | Sex differences in stress responses:Focus on ovarian hormones显示文摘 | Ter Horst G J Wichmann R Gerrits M | 2009 | Physiology and Behavior2009，97，2： | 1 |
| 15 | Effect of surface treatment on the shear bond strength of three resin cements to a machinable feldspatic ceramic显示文摘 | Reich SM Wichmann M Frankenberger R | 2005 | J Biomed Mater Res B2005，74，2： | 1 |
| 16 | Measurement of the diffractive cross section and properities of the hadvonic final state显示文摘 | Wichmann R Wandrey C Buckmann A F | 2000 | Biotechnol Bioeng2000，67，： | 1 |
| 17 | Prolactin administration following hemorrhagic shock improves macrophage cytokine release capacity and decreases mortality from subsequent sepsis显示文摘 | Zellweger R Zhu X-H Wichmann MW | 1996 | Immunol1996，157，： | 1 |
| 18 | Antiparkinsonian and behavioral effects of inactivation of the substantia nigra pars reticulata in hemiparkinsonian primates显示文摘 | Wichmann T Kliem M A DeLong M R | 2001 | Exp Neurol2001，167，2： | 1 |
| 19 | Fast-track rehabilitation in elective colorectal surgery patients: a prospective clinical and immuno- logical single-centre study显示文摘 | Wichmann MW Eben R Angele MK | 2007 | ANZ J Surg2007，77，7： | 1 |
| 20 | Fast-track rehabililation in elective colorectal surgery patients: a prospective clinical and immuno- logical single-centre study 显示文摘 | Wichmann MW Eben R Angele MK | 2007 | ANZ J Surg2007，77，7： | 1 |
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