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Multicenter Study
. 2025 Apr;23(5):766-775.
doi: 10.1016/j.cgh.2024.07.048. Epub 2024 Oct 28.

Multimodal Pancreatic Cancer Detection Using Methylated DNA Biomarkers in Pancreatic Juice and Plasma CA 19-9: A Prospective Multicenter Study

Megan M L Engels  1 , Calise K Berger  2 , Douglas W Mahoney  3 , Sanne A Hoogenboom  1 , Dhruv Sarwal  2 , Derk C F Klatte  1 , Jaime De La Fuente  2 , Sonal Gandhi  2 , William R Taylor  2 , Patrick H Foote  2 , Karen A Doering  2 , Adriana M Delgado  2 , Kelli N Burger  3 , Barham K Abu Dayyeh  2 , Aliana Bofill-Garcia  2 , Bhaumik Brahmbhatt  4 , Vinay Chandrasekhara  2 , Ferga C Gleeson  2 , Victoria Gomez  4 , Vivek Kumbhari  4 , Ryan J Law  2 , Frank J Lukens  4 , Massimo Raimondo  4 , Elizabeth Rajan  2 , Andrew C Storm  2 , Eric J Vargas Valls  2 , Jeanin E van Hooft  5 , Michael B Wallace  6 , John B Kisiel  2 , Shounak Majumder  7
Affiliations
Multicenter Study

Multimodal Pancreatic Cancer Detection Using Methylated DNA Biomarkers in Pancreatic Juice and Plasma CA 19-9: A Prospective Multicenter Study

Megan M L Engels et al. Clin Gastroenterol Hepatol. 2025 Apr.

Abstract

Background and aims: In previous studies, methylated DNA markers (MDMs) have been identified in pancreatic juice (PJ) for detecting pancreatic ductal adenocarcinoma (PDAC). In this prospective multicenter study, the sensitivity and specificity characteristics of this panel of PJ-MDMs was evaluated standalone and in combination with plasma carbohydrate antigen 19-9 (CA 19-9).

Methods: Paired PJ and plasma were assayed from 88 biopsy-proven treatment-naïve PDAC cases and 134 controls (53 with normal pancreas, 23 with chronic pancreatitis [CP], 58 with intraductal papillary mucinous neoplasm). Bisulfite-converted DNA from buffered PJ was analyzed using long-probe quantitative amplified signal assay targeting 14 MDMs (NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4) and a reference gene (methylated B3GALT6). Logistic regression was used to fit the previously identified 3-MDM PJ panel (FER1L4, C13orf18, and BMP3). Discrimination accuracy was summarized using area under the receiver-operating characteristic curve (AUROC) with corresponding 95% confidence interval (CI).

Results: Methylated FER1L4 had the highest individual AUROC of 0.83 (95% CI, 0.78-0.89). The AUROC for the 3-MDM PJ + plasma CA 19-9 model (0.95; 95% CI, 0.92-0.98) was higher than both the 3-MDM PJ panel (0.87; 95% CI, 0.82-0.92)) and plasma CA 19-9 alone (0.91; 95% CI, 0.87-0.96) (P = .0002 and .0135, respectively). At a specificity of 88% (95% CI, 81%-93%), the sensitivity of this model was 89% (95% CI, 80%-94%) for all PDAC stages and 83% (95% CI, 64%-94%) for stage I/II PDAC.

Conclusions: A panel combining PJ-MDMs and plasma CA 19-9 discriminates PDAC from both healthy and disease control groups with high accuracy. This provides support for combining PJ and blood-based biomarkers for enhancing diagnostic sensitivity and successful early PDAC detection.

Keywords: Biomarkers; Carcinoma; Early Detection of Cancer; Liquid Biopsy; Pancreatic Ductal; Pancreatic Neoplasms; Tumor.

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Conflict of interest statement

Conflict of Interest Statement and Disclosures:

Mayo Clinic and Exact Sciences have an intellectual property development agreement. Drs. Majumder, Kisiel and Messrs. Taylor & Mahoney are listed as inventors under this agreement and could share potential future royalties as employees of Mayo Clinic. Dr. Wallace is a consultant for Cosmo/Aries Pharmaceuticals, Verily, Boston Scientific, Endiatix, Intervenn, AlphaMed UAE, Fujifilm, and ClearNote; research grants with Fujifilm, Boston Scientific, Olympus, Medtronic, Ninepoint Medical Cosmo/Aries Pharmaceuticals; Stock Options with Virgo Inc.; consulting on behalf of Mayo Clinic, Boston Scientific, Microtek, Generalpayments/Minor Food and Beverage, and Cook Medical. Dr. Abu Dayyeh is a consultant and receives reserach support from Boston Scientific, Medtronic and Consultant Olympus. Dr. Law is a consultant for Boston Scientific, Medtronic, Conmed and receives research support from WL Gore and Olympus. The other authors of this manuscript have no conflicts of interest to declare. The abstract summarizing preliminary results from this study was presented at Digestive Disease Week 2023 in Chicago, IL.

References

    1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians 2023;73:17–48. - PubMed
    1. Huang J, Lok V, Ngai CH, et al. Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer. Gastroenterology 2021;160:744–754. - PubMed
    1. Vege SS, Ziring B, Jain R, et al. American Gastroenterological Association Institute Guideline on the Diagnosis and Management of Asymptomatic Neoplastic Pancreatic Cysts. Gastroenterology 2015;148:819–22; quize12-3. - PubMed
    1. Tanaka M, Fernández-Del Castillo C, Kamisawa T, et al. Revisions of International Consensus Fukuoka Guidelines for the Management of IPMN of the Pancreas. Pancreatology 2017;17:738–753. - PubMed
    1. Del Chiaro M, Besselink M, Scholten L, et al. European Evidence-Based Guidelines on Pancreatic Cystic Neoplasms. Gut 2018;67:789–804. - PMC - PubMed