A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer
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Background: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. Methods: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. Results: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19–9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02). Conclusions: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
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Biomarker panels often build upon CA 19-9 and demonstrate improved performance in early-stage disease compared with CA 19-9 alone.
“Such biomarker “panels” often build upon CA 19-9 and demonstrate improved performance in early-stage disease compared with CA 19-9 alone.40–43”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [41]
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- Authors
- Fahrmann, J. F., Bantis, L. E., Capello, M., Scelo, G., Dennison, J. B., Patel, N., Murage, E., Vykoukal, J., Kundnani, D. L., Foretova, L., Fabianova, E., Holcatova, I., Janout, V., Feng, Z., Yip-Schneider, M., Zhang, J., Brand, R., Taguchi, A., Maitra, A., Brennan, P., Max Schmidt, C., & Hanash, S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- International Agency for Research on Cancer (IARC), Lyon, France
- Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
- Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia
- Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
- Faculty of Medicine, Palacky University, Olomouc, Czech Republic
- Indiana University Indianapolis (US)
- University of Pittsburgh (US)
- Centre international de recherche sur le cancer (FR)
- Department Surgery, Indiana University School of Medicine, Indianapolis, IN
- Corresponding author
- Hanash, Samir
- ORCID
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-08-18
- Volume
- 111
- Issue
- 4
- Pages
- 372-379
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC6449169
- OpenAlex
- W2885196877
- Cited by
- 115
- References
- 33
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 10 · 2023: 15 · 2022: 16 · 2021: 24 · 2020: 15 · 2019: 14 · 2018: 1
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Cancer Institute Early Detection Network
- Pancreatic Cancer Action Network
- Cancer- Lustgarten Foundation (SU2C-AACR-DT25-17)
- National Institutes of Health (IR32CA209366-01, 1R21CA209366-01, 1U01CA200468, 1U01CA196403, R03 CA123546-02)
- National Cancer Institute
- Development of Research Organization of the Ministry of Health of the Czech Republic (MMCI, 00209805, 9422-3, 8090-3)
- Epidemiological Study on Pancreatic Cancer, Regional Authority of Public Health in Banska Bystrica (MZSR2007/17-RUVZBB-02)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic ductal adenocarcinoma, early-stage cancer detection, CA19-9, LRG1, TIMP-1, lysophosphatidylcholine, intraductal papillary mucinous neoplasm, benign pancreatic cysts
- MeSH terms
- Adenocarcinoma, Mucinous, Carcinoma, Papillary, Follow-Up Studies, Humans, Neoplasm Invasiveness, Neoplasm Staging, Pancreatic Neoplasms, Biomarkers, Tumor, Case-Control Studies, Carcinoma, Pancreatic Ductal, Metabolome, Transcriptome
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