Diagnostic correlation between the expression of the DNA repair enzyme N-methylpurine DNA glycosylase and esophageal adenocarcinoma onset: a retrospective pilot study
Autor: | Z M, Zaïr, G E, Johnson, A P, Griffiths, G J, Jenkins |
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Rok vydání: | 2012 |
Předmět: |
Cell Nucleus
Metaplasia DNA Repair Esophageal Neoplasms Pilot Projects Adenocarcinoma DNA Glycosylases Barrett Esophagus Cell Transformation Neoplastic Kidney Tubules Parietal Cells Gastric Case-Control Studies Mesangial Cells Biomarkers Tumor Disease Progression Humans Lymph Nodes RNA Messenger Intestinal Mucosa Precancerous Conditions Early Detection of Cancer Neoplasm Staging Retrospective Studies |
Zdroj: | Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 26(6) |
ISSN: | 1442-2050 |
Popis: | EAC in its early stages, when it can potentially be cured, is rarely symptomatic and is associated with high mortality rates because in part of late-stage diagnosis. Given that DNA repair is an important contributory factor of early-stage malignancy, our study focused on the expression of the base excision repair enzyme N-methylpurine DNA glycosylase (MPG) in EAC disease onset. MPG messenger RNA (mRNA) expression levels were determined using quantitative reverse transcriptase polymerase chain reaction from a maximum of 72 patient samples. Immunohistochemistry was further utilized for the detection of MPG protein, and semiquantitative analysis performed using an H-score approach was carried out on a total of 130 archival tissue samples of different esophageal pathologies. Nuclear localized MPG protein was detected in all nonmalignant tissues derived from the enterohepatic system, with H-score values of 3.9-5.5 ± 0.4-1.0. In cancerous tissues derived from the enterohepatic system, a 9.5-fold increase in the level of MPG mRNA expression was specifically observed in the malignant regions located within the esophagus region. Further analysis revealed a 9- and 14-fold increase in MPG mRNA expression in EAC tumor, node, metastasis stages II and III, respectively, suggesting MPG expression to correlate with EAC disease progression. Immunohistochemistry analysis further showed a sevenfold significant increase in MPG protein expression in EAC tissues. Intriguingly, there was a fivefold significant decrease in nuclear localized MPG protein expression in tissues derived from Barrett's esophagus and low-grade dysplasia. Such findings highlight a complex regulatory pattern governing DNA glycosylase base excision repair initiation, as normal tissue undergoes Barrett's metaplasia and later dedifferentiates to EAC. Indeed, disease-stage-specific alterations in the expression of MPG may highlight a potential role for MPG in determining EAC onset and thus potentially be of clinical relevance for early disease detection and increased patient survival. |
Databáze: | OpenAIRE |
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