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Pancreatic Juice Mutation Concentrations Can Help Predict the Grade of Dysplasia in Patients Undergoing Pancreatic Surveillance
Open accessPublished version of a preprint
Abstract
Purpose: The measurement of mutations in pancreatic juice samples collected from the duodenum during endoscopic ultrasound (EUS) may improve the diagnostic evaluation of patients undergoing pancreatic surveillance. Our aim was to evaluate the accuracy of using pancreatic juice mutation concentrations to predict the presence and histologic grade of neoplasia in the pancreas. Experimental Design: Digital next-generation sequencing (NGS) of pancreatic juice DNA using a targeted 12-gene panel was performed on 67 patients undergoing pancreatic evaluation during EUS, including patients with pancreatic ductal adenocarcinoma, patients who subsequently underwent pancreatic resection for precursor lesions, patients undergoing surveillance for their familial/inherited susceptibility to pancreatic cancer, and normal pancreas disease controls. Results: Patients with pancreatic cancer or high-grade dysplasia as their highest grade lesion had significantly higher pancreatic juice mutation concentrations than all other subjects (mean/SD digital NGS score; 46.6 ± 69.7 vs. 6.2 ± 11.6, P = 0.02). Pancreatic juice mutation concentrations distinguished patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 72.2% sensitivity and 89.4% specificity [area under the curve (AUC) = 0.872]. Mutant TP53/SMAD4 concentrations could distinguish patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 61.1% sensitivity and 95.7% specificity (AUC = 0.819). Among 31 high-risk individuals under surveillance, 2 of the 3 individuals with most abnormal pancreatic juice mutation profiles also had the most abnormalities on pancreatic imaging. Conclusions: Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance. Clin Cancer Res; 24(12); 2963–74. ©2018 AACR. See related commentary by Lipner and Yeh, p. 2713
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“In passing, it also needs to be stated that, although blood remains the most commonly studied biospecimen for early detection, many of the analytes are also present in other proximate samples, including pancreatic juice,53,54 stool,55 urine,56,57 saliva,58 and pancreatic cyst fluid.59”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [54]
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Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · cited 20×
“As the most important goal of pancreatic surveillance is to detect evidence of pancreatic cancer or high-grade dysplasia, patients were grouped into those with pancreatic cancer or high-grade dysplasia (PanIN-3 or in IPMN) versus all others (disease controls, those under surveillance, and those with low-grade dysplasi…”
BackgroundInfluentialVincent, A., Herman, J. M., Schulick, R., Hruban, R. H., & Goggins, M. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62307-0 · Cited by 2,678
Self-citationInternational consensus guidelines 2012 for the management of IPMN and MCN of the pancreas
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DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1
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Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment
Wood, L. D., Canto, M. I., Jaffee, E. M., & Simeone, D. M. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.03.056 · Cited by 918
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Self-citationThe Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival
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Metadata
- Authors
- Suenaga, M., Yu, J., Shindo, K., Tamura, K., Almario, J. A., Zaykoski, C., Witmer, P. D., Fesharakizadeh, S., Borges, M., Lennon, A.-M., Shin, E.-J., Canto, M. I., & Goggins, M.
- Affiliations
- Johns Hopkins University (US)
- 2Center for Inherited Disease Research (CIDR), Baltimore, Maryland.
- Corresponding author
- Goggins, Michael
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2018-06-14
- Volume
- 24
- Issue
- 12
- Pages
- 2963-2974
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC6435263
- OpenAlex
- W2782485244
- Cited by
- 81
- References
- 51
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 7 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 14 · 2018: 8
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA062924, R01CA176828)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK089502)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic juice, circulating tumor DNA, pancreatic cancer surveillance, pancreatic dysplasia, histologic grade prediction, TP53 mutation, SMAD4 mutation, endoscopic ultrasound, pancreatic ductal adenocarcinoma, pancreatic precursor lesions
- MeSH terms
- Cell-Free Nucleic Acids, Aged, Aged, 80 and over, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Mutation, Pancreas, Pancreatic Juice, Pancreatic Neoplasms, Population Surveillance, ROC Curve, Biomarkers, Tumor, High-Throughput Nucleotide Sequencing, Neoplasm Grading
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