| Title |
Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for pancreatic adenocarcinoma
|
|---|---|
| Published in |
Clinical Epigenetics, November 2016
|
| DOI | 10.1186/s13148-016-0286-2 |
| Pubmed ID | |
| Authors |
Stine Dam Henriksen, Poul Henning Madsen, Anders Christian Larsen, Martin Berg Johansen, Asbjørn Mohr Drewes, Inge Søkilde Pedersen, Henrik Krarup, Ole Thorlacius-Ussing |
| Abstract |
Pancreatic cancer has a 5-year survival rate of only 5-7%. Difficulties in detecting pancreatic cancer at early stages results in the high mortality and substantiates the need for additional diagnostic tools. Surgery is the only curative treatment and unfortunately only possible in localized tumours. A diagnostic biomarker for pancreatic cancer will have a major impact on patient survival by facilitating early detection and the possibility for curative treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis, which can cause inactivation of tumour suppressor genes. The aim of this study was to examine promoter hypermethylation in a panel of selected genes from cell-free DNA, as a diagnostic marker for pancreatic adenocarcinoma. Patients with suspected or biopsy-verified pancreatic cancer were included prospectively and consecutively. Patients with chronic/acute pancreatitis were included as additional benign control groups. Based on an optimized accelerated bisulfite treatment protocol, methylation-specific PCR of a 28 gene panel was performed on plasma samples. A diagnostic prediction model was developed by multivariable logistic regression analysis using backward stepwise elimination. Patients with pancreatic adenocarcinoma (n = 95), chronic pancreatitis (n = 97) and acute pancreatitis (n = 59) and patients screened, but negative for pancreatic adenocarcinoma (n = 27), were included. The difference in mean number of methylated genes in the cancer group (8.41 (95% CI 7.62-9.20)) vs the total control group (4.74 (95% CI 4.40-5.08)) was highly significant (p < 0.001). A diagnostic prediction model (age >65, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) had an area under the curve of 0.86 (sensitivity 76%, specificity 83%). The model performance was independent of cancer stage. Cell-free DNA promoter hypermethylation has the potential to be a diagnostic marker for pancreatic adenocarcinoma and differentiate between malignant and benign pancreatic disease. This study brings us closer to a clinical useful diagnostic marker for pancreatic cancer, which is urgently needed. External validation is, however, required before the test can be applied in the clinic. ClinicalTrials.gov, NCT02079363. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 117 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 117 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 22 | 19% |
| Student > Master | 14 | 12% |
| Student > Ph. D. Student | 13 | 11% |
| Other | 11 | 9% |
| Student > Bachelor | 10 | 9% |
| Other | 10 | 9% |
| Unknown | 37 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 39 | 33% |
| Biochemistry, Genetics and Molecular Biology | 13 | 11% |
| Agricultural and Biological Sciences | 5 | 4% |
| Social Sciences | 3 | 3% |
| Nursing and Health Professions | 2 | 2% |
| Other | 7 | 6% |
| Unknown | 48 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 November 2016.
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#20,353,668
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Outputs from Clinical Epigenetics
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Outputs of similar age from Clinical Epigenetics
#22
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