Promoter hypermethylation in plasma-derived cell-free DNA as a prognostic marker for pancreatic adenocarcinoma staging
| Autor: | Stine Dam Henriksen, Inge Søkilde Pedersen, Poul Henning Madsen, Martin Berg Johansen, Anders Christian Larsen, Henrik Krarup, Ole Thorlacius-Ussing |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Pathology Cancer Biology medicine.disease MLH1 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cell-free fetal DNA 030220 oncology & carcinogenesis Pancreatic cancer Internal medicine DNA methylation medicine Adenocarcinoma Biomarker (medicine) Stage (cooking) |
| Zdroj: | International Journal of Cancer. 141:2489-2497 |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.31024 |
| Popis: | Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment. Patients were staged according to the TNM classification. Methylation-specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety-five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51-8.66), 7.00 (95% CI; 5.93-8.07) and 6.77 (95% CI; 5.08-8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88-11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I-III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I-II from stage III-IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell-free DNA promoter hypermethylation has the potential to be blood-based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required. |
| Databáze: | OpenAIRE |
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