ArticleThe American journal of gastroenterology2019
Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing.
Article in The American journal of gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- The Impact of Endoscopic Ultrasound and Multidisciplinary Team Evaluation on the Management of Pancreatic Cystic Lesions.United European gastroenterology journal · 2026Trial
- Multidisciplinary Team Approach for Managing Pancreatic Cysts: Impact, Bias, and Opportunities for Improvement.United European gastroenterology journal · 2026Article
- Gut Microbiota-Brain Axis in Pancreatic Cystic Neoplasms: An Observational Analysis.Pakistan journal of medical sciences · 2025Article
- DNA methylation profile to aid in the diagnosis of pancreatic ductal adenocarcinoma and its role in disease progression.Epigenomics · 2025Review
- Identifying Neoplastic Versus Non-neoplastic Pancreatic Cystic Lesions-What Is the Current Evidence?Digestive diseases and sciences · 2025Review
- Multimodal Pancreatic Cancer Detection Using Methylated DNA Biomarkers in Pancreatic Juice and Plasma CA 19-9: A Prospective Multicenter Study.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2025Article
- The Role of DNA Methylation in Gastrointestinal Disease: An Expanded Review of Malignant and Nonmalignant Gastrointestinal Diseases.Gastroenterology · 2025Review
- Epigenetic dysregulation in pancreatic cancer: emerging biomarkers and clinical applications.Frontiers in epigenetics and epigenomics · 2025Review
- Early detection of pancreatic cancer: Study design and analytical considerations in biomarker discovery and early phase validation studies.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2024Review
- Comparative accuracy of four guidelines to predict high-grade dysplasia or malignancy in surgically resected pancreatic intraductal papillary mucinous neoplasms: Small nuances between guidelines lead to vastly different results.Annals of hepato-biliary-pancreatic surgery · 2024Article
- Diagnostics and Management of Pancreatic Cystic Lesions-New Techniques and Guidelines.Journal of clinical medicine · 2024Review
- Review
- Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms.Clinical epigenetics · 2023Article
- Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment.Cancers · 2022Review
- Molecular Analysis of Pancreatic Cyst Fluid for the Management of Intraductal Papillary Mucinous Neoplasms.Diagnostics (Basel, Switzerland) · 2022Review
- Tissue methylated DNA markers for sporadic pancreatic cancer are strongly associated with familial and genetically predisposed pancreatic cancer.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2022Article
- DNA methylation-based predictors of health: applications and statistical considerations.Nature reviews. Genetics · 2022Review
- Discovery and Validation of Methylated DNA Markers From Pancreatic Neuroendocrine Tumors.Gastro hep advances · 2022Article
- TBX15/miR-152/KIF2C pathway regulates breast cancer doxorubicin resistance via promoting PKM2 ubiquitination.Cancer cell international · 2021Article
- Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions.Cancers · 2021Article
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 1 country.
Funding
Abstract
objectivesPancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND).
methodsFrom an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs.
resultsOf 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.