Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. DNA-Based Analyses
2.3. RNA-Based Analyses
2.4. Proteomic Analyses
2.4.1. One-Dimension Experiments
2.4.2. Two-Dimension Experiments
2.4.3. Western Blot Analysis
2.5. Statistical Analyses
3. Results
3.1. Clinico-Pathological Characteristics of Early-Onset Patients
3.2. Genomic and Methylomic Landscape of PDAC in Early-Onset Patients
3.3. Transcriptomic Landscape in Early-Onset Patients
3.4. Oxidative Stress Damages and Defenses in Early-Onset Patients
3.5. Protein Oxidative Damages in Early-Onset Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cohort Features n = 255 | ||||
---|---|---|---|---|
Age Group | EOP < 55 y.o. (106) | LOP > 70 y.o. (149) | p | |
Sex (n = Men (%)) n = 255 | 46 (43.39%) | 75 (50.33%) | 0.389 ⁱ | |
Age (median (min-max)) n = 255 | 51 (34–55) | 74 (70–88) | <0.0001 ⁱ | |
T n = 255 | 0.841 * | |||
T1 | 4 | 4 | ||
T2 | 16 | 25 | ||
T3 | 86 | 120 | ||
N n = 255 | N0/N1 | 32/74 | 35/141 | 0.292 * |
Tumor differentiation n = 255 | 0.197 * | |||
Well | 35 | 68 | ||
Moderate | 48 | 50 | ||
Poorly | 20 | 27 | ||
Unknown | 3 | 4 | ||
Tumor size n = 238 (mm mean—CI95) | 31.9 (27.8–35) | 33.9 (31.0–36.8) | 0.239 ⁱ | |
Vascular invasion n = 204 (n (%)) | 57 (53.7) | 58 (38.9) | 0.024 ⁱ | |
Perinervous invasion n = 237 (n (%)) | 81 (76.6) | 104 (69.8) | 0.346 ⁱ |
Cohort features n = 255 | Univariate PFS EOP <55 y.o. (106) | Univariate PFS LOP >70 y.o. (149) | Multivariate PFS LOP >70 y.o. (149) | Univariate OS EOP <55 y.o. (106) | Univariate OS LOP > 70 y.o. (149) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Age Group | HR | 95% Ci | p * | HR | 95% Ci | p * | HR | 95%Ci | p * | HR | 95%Ci | p * | HR | 95%Ci | p * |
Sex (Men) | 0.79 | 0.49–1.27 | 0.335 | 0.841 | 0.56–1.26 | 0.405 | 0.956 | 0.58–1.57 | 0.86 | 0.786 | 0.52-.13 | 0.187 | |||
Age | 1.023 | 0.97–1.07 | 0.396 | 0.944 | 0.88–1.00 | 0.084 | 1.013 | 0.96–1.06 | 0.638 | 0.985 | 0.93–1.04 | 0.611 | |||
T | 0.023 | 0.954 | |||||||||||||
T1 | 0.883 | 0.27–2.81 | 0.834 | 0.2 | 0.02–1.42 | 0.11 | 0.326 | 0.04–2.39 | 0.273 | 1.131 | 0.35–3.62 | 0.837 | 0.266 | 0.03–1.89 | 0.189 |
T2 | 0.656 | 0.32–1.32 | 0.24 | 0.583 | 0.32–1.04 | 0.072 | 0.706 | 0.38–1.28 | 0.255 | 0.931 | 0.47–1.83 | 0.837 | 0.716 | 0.42–1.22 | 0.223 |
T3 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | - | 1 | 1 | 1 |
N0/N1 | 1.639 | 0.96–2.79 | 0.071 | 2.697 | 1.52–4.75 | 0.0007 | 2.53 | 1.11–4.54 | 0.002 | 0.571 | 0.32–1.02 | 0.06 | 0.415 | 0.24–0.71 | 0.002 |
Tumor differentiation n = 255 | 0.015 | ||||||||||||||
Well | 0.875 | 0.50–1.50 | 0.634 | 1 | 1 | 1 | 1 | 1 | 1 | 0.942 | 0.52–1.68 | 0.841 | 1 | 1 | 1 |
Moderate | 1 | 1 | 1 | 1.787 | 1.13–2.82 | 0.013 | 1.738 | 1.09–2.76 | 0.02 | 1 | 1 | 1 | 1.18 | 0.76–1.83 | 0.459 |
Poorly | 1.215 | 0.65–2.26 | 0.542 | 1.966 | 1.14–3.38 | 0.015 | 2.14 | 1.23–3.71 | 0.006 | 1.343 | 0.696–2.59 | 0.382 | 1.65 | 0.96–2.83 | 0.068 |
Unknown | 0.841 | 0.20–3.49 | 0.813 | 0.451 | 0.06–3.25 | 0.432 | 0.893 | 0.11–6.77 | 0.913 | 1.525 | 0.46–5.00 | 0.488 | 0.728 | 0.17–2.99 | 0.662 |
Tumor size | 1.005 | 0.99–1.01 | 0.436 | 1.008 | 0.99–1.02 | 0.147 | 1.003 | 0.98–1.02 | 0.747 | 1.008 | 0.99–1.01 | 0.122 | |||
Vascular invasion | 1.43 | 0.99–2.0 | 0.054 | 1.35- | 0.88–1.45 | 0.322 | 1.508 | 1.03–2.19 | 0.032 | 1.064 | 0.83–1.36 | 0.619 | |||
Perinervous invasion | 1.246 | 0.72–2.13 | 0.425 | 1.42 | 0.98–2.07 | 0.061 | 0.999 | 0.57–1.75 | 0.999 | 1.295 | 0.90–1.85 | 0.158 |
Mutations | Multi-Centric | ICGC | TCGA | ||||||
---|---|---|---|---|---|---|---|---|---|
EOP (53) | LOP (89) | p * | EOP (39) | LOP (110) | p * | EOP (27) | LOP (55) | p * | |
KRAS n = (%) | 48 (90.5) | 81 (91) | 0.832 | 29 (74.3) | 87 (79.1) | 0.653 | 25 (92.6) | 50 (90.9) | 0.704 |
TP53 n = (%) | 37 (69.8) | 63 (70.8) | 0.946 | 19 (48.7) | 70 (63.6) | 0.129 | 23 (85.2) | 39 (70.9) | 0.183 |
CDKN2A n = (%) | 11 (20.7) | 14 (15.7) | 0.594 | 4 (10.2) | 15 (13.6) | 0.781 | 16 (59.2) | 33 (60) | 1.00 |
SMAD4 n = (%) | 5 (9.4) | 22 (24.7) | 0.043 | 7 (17.9) | 27 (24.5) | 0.507 | 12 (44.4) | 22 (40) | 0.812 |
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Raffenne, J.; Martin, F.A.; Nicolle, R.; Konta, M.; Blum, Y.; Torrisani, J.; Puleo, F.; Bachet, J.B.; Svrcek, M.; Bardier-Dupas, A.; et al. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features. Cancers 2021, 13, 1234. https://doi.org/10.3390/cancers13061234
Raffenne J, Martin FA, Nicolle R, Konta M, Blum Y, Torrisani J, Puleo F, Bachet JB, Svrcek M, Bardier-Dupas A, et al. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features. Cancers. 2021; 13(6):1234. https://doi.org/10.3390/cancers13061234
Chicago/Turabian StyleRaffenne, Jérôme, Fernando A. Martin, Rémy Nicolle, Marina Konta, Yuna Blum, Jérôme Torrisani, Francesco Puleo, Jean Baptiste Bachet, Magali Svrcek, Armel Bardier-Dupas, and et al. 2021. "Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features" Cancers 13, no. 6: 1234. https://doi.org/10.3390/cancers13061234