Long Interspersed Nuclear Element-1 Hypomethylation and Oxidative Stress: Correlation and Bladder Cancer Diagnostic Potential
| Autor: | Chanchai Boonla, Piyaratana Tosukhowong, Apiwat Mutirangura, Maturada Patchsung, Passakorn Amnattrakul, Thasinas Dissayabutra |
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| Rok vydání: | 2012 |
| Předmět: |
Male
lcsh:Medicine medicine.disease_cause Antioxidants Protein Carbonylation Oxidative Damage Combined bisulfite restriction analysis Molecular Cell Biology Basic Cancer Research lcsh:Science skin and connective tissue diseases Cellular Stress Responses Aged 80 and over Bladder Cancer and Urothelial Neoplasias of the Urinary Tract Multidisciplinary Methylation Middle Aged Bladder Cancer Blood proteins Signaling Cascades Oncology DNA methylation Medicine Female Epigenetics DNA modification Research Article Signal Transduction Adult Urology Urinary system Biology Stress Signaling Cascade Genetics Cancer Detection and Diagnosis Early Detection medicine Humans Aged Bladder cancer lcsh:R Cancers and Neoplasms DNA Methylation medicine.disease Molecular biology Oxidative Stress Genitourinary Tract Tumors Long Interspersed Nucleotide Elements Urinary Bladder Neoplasms lcsh:Q Gene expression Oxidative stress |
| Zdroj: | PLoS ONE, Vol 7, Iss 5, p e37009 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Although, increased oxidative stress and hypomethylation of long interspersed nuclear element-1 (LINE-1) associate with bladder cancer (BCa) development, the relationship between these alterations is unknown. We evaluated the oxidative stress and hypomethylation of the LINE-1 in 61 BCa patients and 45 normal individuals. To measure the methylation levels and to differentiate the LINE-1 loci into hypermethylated, partially methylated and hypomethylated, peripheral blood cells, urinary exfoliated cells and cancerous tissues were evaluated by combined bisulfite restriction analysis PCR. The urinary total antioxidant status (TAS) and plasma protein carbonyl content were determined. The LINE-1 methylation levels and patterns, especially hypomethylated loci, in the blood and urine cells of the BCa patients were different from the levels and patterns in the healthy controls. The urinary TAS was decreased, whereas the plasma protein carbonyl content was increased in the BCa patients relative to the controls. A positive correlation between the methylation of LINE-1 in the blood-derived DNA and urinary TAS was found in both the BCa and control groups. The urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content provided the best diagnostic potential for BCa prediction. Based on post-diagnostic samples, the combination test improved the diagnostic power to a sensitivity of 96% and a specificity of 96%. In conclusion, decreased LINE-1 methylation is associated with increased oxidative stress both in healthy and BCa subjects across the various tissue types, implying a dose-response association. Increases in the LINE-1 hypomethylation levels and the number of hypomethylated loci in both the blood- and urine-derived cells and increase in the oxidative stress were found in the BCa patients. The combination test of the urinary hypomethylated LINE-1 loci and the plasma protein carbonyl content may be useful for BCa screening and monitoring of treatment. |
| Databáze: | OpenAIRE |
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