Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers
| Autor: | Lisa Spaller, Fabian Schröder, Judith Stift, Ruth Exner, Walter Pulverer, Laura Woltering, Fritz Wrba, Martina Diem, Brigitte Wolf, Michael Bergmann, Martin Schreiber, Markus Sonntagbauer, Gerda Egger, Andreas Weinhäusel |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Colorectal cancer Biology 03 medical and health sciences 0302 clinical medicine CDKN2A Biomarkers Tumor medicine Rectal Adenocarcinoma Humans rectal cancer Molecular Diagnostics CpG methylator phenotype Cyclin-Dependent Kinase Inhibitor p16 Aged Oligonucleotide Array Sequence Analysis 030304 developmental biology Aged 80 and over 0303 health sciences DNA methylation CIMP CpG Island Methylator Phenotype Rectal Neoplasms epigenetic biomarker DNA Neoplasm Methylation Middle Aged Prognosis medicine.disease Survival Analysis Neoplasm Proteins 3. Good health Oncology CpG site 030220 oncology & carcinogenesis Cancer research CpG Islands Female DNA microarray |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. Results: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. Conclusions: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer. |
| Databáze: | OpenAIRE |
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