Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma
Abstract
:1. Introduction
2. Traditional Serum Biomarkers
2.1. CA 19-9 for Detecting Pancreatic Cancer
2.2. CA 19-9 for Determining Patient Prognosis
3. Novel Serum Biomarkers
3.1. DNA Methylation: Detection and Prognosticating
3.2. Cell-Free Nucleosomes: Detection
3.3. MicroRNAs: Detection
3.4. Cell-Free Tumor DNA: Early Response Assessment
3.5. Multimarker Panels for Detection
3.6. Multimarker Panels: Prognostication
4. Imaging Biomarkers
4.1. Imaging Markers for Detecting Pancreatic Cancer
4.2. Computed Tomography Imaging Markers for Predicting Patient Outcome
4.3. Positron Emission Tomography Marker for Predicting Patient Response
4.4. Functional Magnetic Resonance Parameters as Predictive Markers
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Patient Groups | Sensitivity (%) | Specificity (%) | PPV | NPV |
---|---|---|---|---|
Symptomatic | 79–81 | 82–90 | 72 | 81–96 |
Asymptomatic | 100 | 98.5 | 0.03–0.9 | - |
CA 19-9; CEA | Mean Survival (months) |
---|---|
≤75 U/mL; ≤3 ng/mL | 33.3 |
>75 U/mL; ≤3 ng/mL | 28.5 |
or | |
≤75 U/mL; >3 ng/mL | |
>75 U/mL; >3 ng/mL | 23.9 |
References | Marker Class | Markers | Comments |
---|---|---|---|
[26] | DNA Methylation | IL-10_ P348, LCN2_P86, ZAP70_P220, AIM2_P624 and TAL1_P817 | Sen: 72%; Spec: 70% for detecting PDAC. Never-smoked population |
[27] | DNA Methylation | TNFRSCF10C, ACIN1 | Hypermethylation indicates shorter survival |
DNA Methylation | Line-1 and ALU repeats | PDAC patients have decreased methylation in ALU and Line-1 CpG repeats | |
[28] | Cell Free Nucleosomes | 5MC, H2AZ, H2A1.1, H3K4Me2, CA 19-9 | AUC: 0.98; Sen: 92%; Spec: 90% for detecting PDAC |
[29] | MicroRNA | miR-223 | Elevated miR-223 increased risk for PDAC |
[30] | Cell Free DNA | KRAS mutation | 77% concordant between actual biopsy and liquid biopsy in detecting mutation |
References | Markers (Protein) | Comments |
---|---|---|
[31] | CA 19-9, ICAM-1, OPG | Sen: 78% and Spec: 94% in detecting pancreatic cancer |
[32] | CA 19-9, OPN, CHI3L1 | Sen: 93% in detecting pancreatic cancer Studied in stage II/III patients |
[33] | CA 19-9, CEA, Cyfra 21-1 | Increased sensitivity of detection at high level of specificity in asymptomatic subjects Studied in prostate, lung, colorectal, and ovarian screening study population |
[34] | CA 19-1, CA 242, CA 125, CEA | Sen: 90% and Spec: 94% Studied in patients undergoing chemoradiation |
Imaging Finding | Sensitivity (%) | Specificity (%) | Accuracy |
---|---|---|---|
Focal mass | 75 | 84 | 0.81 |
Pancreatic duct dilation | 50 | 78 | 0.7 |
Duct interruption | 45 | 82 | 0.71 |
Upstream atrophy | 45 | 96 | 0.81 |
Contour abnormality | 15 | 92 | 0.7 |
CBD dilation | 5 | 92 | 0.67 |
Reference | Patient Population | Contrast Phase: ∆HU from Unenhanced CT | Survival |
---|---|---|---|
[57] | Unresectable | Arterial: ≥28 | 20.8 vs. 10.9 months |
Unresectable | Portovenous: ≥34 | 20.8 vs. 10.9 months | |
Unresectable | Delayed: ≥36 | 20.8 vs. 11.8 months | |
[57] | Resectable | Arterial: ≥48 | 60.8 vs. 18.3 months |
Resectable | Portovenous: ≥56 | 60.8 vs. 18.3 months | |
Resectable | Delayed: ≥57 | 60.8 vs. 16.4 months | |
[58] | Unresectable (Pancreatic mass enhancement) | Arterial: ≥31.5 | Sen: 62.8%; Spec: 91.3% for predicting response to chemotherapy |
Unresectable (Liver mass enhancement) | Arterial: ≥18 | Sen: 76%; Spec: 85.7% for predicting response to chemotherapy |
Reference | Patient Population/Therapy | SUV Threshold | Overall Survival |
---|---|---|---|
[63] | Stage I/II:Curative Resection | <5 | 28 vs. 16 months |
[64] | Locally Advanced/Chemoradiation | ≤5.5 | 16.6 vs. 12.6 months |
[66] | Locally Advanced/Chemoradiation | ≥50% decrease following therapy | 1 year survival of 87% vs. 28% |
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Chang, J.C.; Kundranda, M. Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma. Int. J. Mol. Sci. 2017, 18, 667. https://doi.org/10.3390/ijms18030667
Chang JC, Kundranda M. Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma. International Journal of Molecular Sciences. 2017; 18(3):667. https://doi.org/10.3390/ijms18030667
Chicago/Turabian StyleChang, John C., and Madappa Kundranda. 2017. "Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma" International Journal of Molecular Sciences 18, no. 3: 667. https://doi.org/10.3390/ijms18030667