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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 | Metastatic prostate cancercomplicated with chronic disseminated intravascular coagulopa-thy causing acute renal failure,mimicking thrombotic thrombo-cytopenic purpura and hemolytic uremic syndrome:pathomech-anism,differential diagnosis and therapy related to a case显示文摘 | Deme D Ragán M Kalmár K | 2010 | Magy Onkol2010，54，4： | 1 |
| 3 | Biodegradation of benzidine based dye direct blue-6 by pseudomonas desmolyticum NCIM 2112显示文摘 | S D Kalme G K Parshetti S U Jadhav | 2006 | Bioresource Technology2006，1，： | 1 |
| 4 | AMP-activated pro- tein kinase: ancient-energy gauge provides clues to mo dern understanding of metabolism显示文摘 | Kalm BB Alquier T Carling D | 2005 | Cell Metab2005，1，1： | 1 |
| 5 | Personal use of hair dyes and risk of bladder cancer: A meta-analysis of epidemiologic data显示文摘 | Kelsh M A Alexander D D Kalmes R M | 2008 | Cancer Causes Control2008，19，6： | 1 |
| 6 | Biodegradation of benzidine based dye Direct Blue-6 by Psettdomonas desmolyticum NCIM 2112显示文摘 | KALME S D PARSHETTI G K JADHAV S U | 2007 | Bioresource Technology2007，98，7： | 1 |
| 7 | AMP-activated prorein kinase :Ancient energy gauge provides clues to modern understanding of metabolism 显示文摘 | Kalm BB Alquier T Calling D | 2005 | Cell Metab2005，1，： | 1 |
| 8 | A serine-kinase associated with the p127-1(2) gl tumour suppressor of Drosophila may regulate the binding of p127 to nonmuscle myosin Ⅱ heavy chain and the attachment of p127 to the plasma membrane显示文摘 | Kalmes A Merdes G Neumann B Strand D Mechler B M | 1996 | J Cell Sci1996，109，6： | 1 |
| 9 | Targeted radiopharmaceutical therapy for advanced lung cancer: phase I trial of rhenium Re188 p2045, a somatostatin analog显示文摘 | Edelman M J Clamon G Kalm D | 2009 | J Thorac Oncol2009，4，12： | 1 |
| 10 | Postprandial gastrointestinal hormone production is different, depending on the type of construction following total gastrectomy显示文摘 | Kalm 6 r K N 6 meth J Kelemen D etal | 2006 | Ann Surg2006，243，4： | 1 |
| 11 | Decolourization of azo dye methyl red by Saccharomyces cerevisiae MTCC463显示文摘 | Jadhav J P Parshetti G K Kalme S D | 2007 | Chemosphere2007，68，2： | 1 |
| 12 | Clay minerals and their paleoenviromental interpretation in the Baoji loess section显示文摘 | KALM V E RUTTER N W ROKOSH C D | 1996 | Southern Loess Plateau1996，27，1： | 1 |
| 13 | Personal use of hair dyes and risk of bladder cancer: A meta-analysis of epidemiologic data 显示文摘 | Kelsh M A Alexander D D Kalmes R M | 2008 | Cancer Cauls and Control2008，19，6： | 1 |
| 14 | Clay minerals and their paleoenvironmental interpretations in the Baoji loess section, southern Loess Plateau, China显示文摘 | Kalm V E Rutter N W Rokosh C D | 1996 | Catena1996，27，： | 1 |
| 15 | Decolourization of azo dye methyl red by Saccharomyces cerevisiae MTCC 463显示文摘 | Jadhav J P Parshetti G K Kalme S D | | 0，，02： | 1 |
| 16 | The Broad-Complex directly controls a tissue-specific response to the steroid hormone ecdysone at the onset of Drosophila metamorphosis显示文摘 | Von Kalm L Crossgrove K Von Seggern D | 1994 | EMBO J1994，13，15： | 1 |
| 17 | Biodegradation of methyl red by Galactomyces geotrichum MTCC 1360显示文摘 | Jadhav S U Kalme S D Govindwar S P | | 0，，02： | 1 |
| 18 | Biodegradation of Reactive blue-25 by Aspergillus ochraceus NCIM-1146 显示文摘 | PARSHETTI G K KALME S D | 2007 | Bioresource Technology2007，98，： | 1 |
| 19 | AMP-activated protein kinase : ancientenergy gauge provides clues to modern understanding of metabolism 显示文摘 | Kalm BB Alquier T Carling D | 2005 | Cell Metab2005，1，1： | 1 |
| 20 | Postprandial gastroin- testinal hormone production is different,depending on the type of reconstruction following total gastrectomy显示文摘 | Kalm d r K N e meth J Kelemen D et aI | 2006 | Ann Surg2006，243，： | 1 |
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