A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Participants
2.2. Candidate Protein Selection and Measurement
2.3. Statistical Analyses
3. Results
3.1. Patient Characteristics
3.2. Protein Analysis and Selection of Final Candidates
3.3. Model Development and Cross Validation
3.4. Model Performance in Sub-Populations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CA 19-9 | Carbohydrate Antigen 19-9 |
CI | Confidence Interval |
CPB1 | Carboxypeptidase B1 |
CTSD | Cathepsin D |
GPNMB | Glycoprotein Non-Metastatic Melanoma Protein B |
ICAM1 | Intracellular Adhesion Molecule 1 |
KLK10 | Kallikrein Related Peptidase 10 |
LTBP2 | Latent Transforming Growth Factor-Beta Binding Protein 2 |
MERTK | Mer Tyrosine Kinase |
MMP-9 | Matrix Metalloproteinase 9 |
NET | Neutrophil Extracellular Trap |
PDAC | Pancreatic Ductal Adenocarcinoma |
PLA2G1B | Phospholipase A2 group 1B |
TGF-β1 | Transforming Growth Factor-Beta 1 |
THBS1 | Thrombospondin 1 |
TIMP1 | Tissue Inhibitor of Metalloproteinase 1 |
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Clinical Variable | All (n = 623) | Cases (n = 128) | Controls (n = 495) |
---|---|---|---|
Age, median (min-max) | 64 (40–95) | 68 (46–95) | 63 (40–83) |
CA 19-9 U/mL, median (min-max) | 10 (0.6–1000) * | 78 (0.6–1000) | 9 (0.6–70) |
Sex male, n (% of column heading) | 244 (39%) | 69 (54%) | 175 (35%) |
PDAC Stage I, n (% of column heading) | 88 (14%) | 88 (69%) | N/A |
PDAC Stage II, n (% of column heading) | 40 (6%) | 40 (31%) | N/A |
White (% of column heading) | 481 (77%) | 52 (41%) | 429 (86%) |
Not White (% of column heading) | 28 (4%) | 4 (3%) | 28 (22%) |
Not reported (% of column heading) | 114 (18%) | 72 (56%) | 42 (33%) |
Marker | p-Value (Controls vs. Cases) | Concentration Means, Cases (CA19-9, U/mL; All Others, ng/mL) | Concentration Means, Controls (CA19-9, U/mL; All Others, ng/mL) | Sensitivity at 98% Specificity, % (95% CI) |
---|---|---|---|---|
CA 19-9 | <0.001 | 248 | 12 | 65 (57–73) |
ICAM1 | <0.001 | 363 | 161 | 52 (44–61) |
TIMP1 | <0.001 | 657 | 375 | 48 (39–56) |
CTSD | <0.001 | 646 | 333 | 31 (23–39) |
LTBP2 | <0.001 | 215 | 133 | 12 (6–17) |
CPB1 | <0.001 | 8139 | 3199 | 6 (2–10) |
THBS1 | 0.220 | 30613 | 28844 | 2 (0–5) |
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Palma, N.A.; Lucas, A.L.; Katona, B.W.; Athanasiou, A.; Kureshi, N.M.; Ford, L.; Keller, T.; Weber, S.; Schiess, R.; King, T.; et al. A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals. Cancers 2025, 17, 1866. https://doi.org/10.3390/cancers17111866
Palma NA, Lucas AL, Katona BW, Athanasiou A, Kureshi NM, Ford L, Keller T, Weber S, Schiess R, King T, et al. A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals. Cancers. 2025; 17(11):1866. https://doi.org/10.3390/cancers17111866
Chicago/Turabian StylePalma, Norma A., Aimee L. Lucas, Bryson W. Katona, Alcibiade Athanasiou, Natasha M. Kureshi, Lisa Ford, Thomas Keller, Stephen Weber, Ralph Schiess, Thomas King, and et al. 2025. "A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals" Cancers 17, no. 11: 1866. https://doi.org/10.3390/cancers17111866
APA StylePalma, N. A., Lucas, A. L., Katona, B. W., Athanasiou, A., Kureshi, N. M., Ford, L., Keller, T., Weber, S., Schiess, R., King, T., Simeone, D. M., & Brand, R. (2025). A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals. Cancers, 17(11), 1866. https://doi.org/10.3390/cancers17111866