Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma
Abstract
:Simple Summary
Abstract
1. Background
2. Methods
2.1. Patients and Tumor Samples
2.2. Immunohistochemistry (IHC) and Analysis
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A. PANCALYZE Study Group
- 1 Department of General, Visceral and Cancer Surgery, University Hospital of Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
- 3 Department of General and Visceral Surgery, Sana Klinikum Lichtenberg, Berlin, Germany
- 4 Department of General and Visceral Surgery, Klinikum Ernst von Bergmann, Potsdam, Germany
- 5 Department of General and Visceral Surgery, Ostalb-Klinikum Aalen, Aalen, Germany
- 6 Department of General and Visceral Surgery, Carl-von-Basedow Klinikum Saalekreis, Merseburg, Germany
- 7 Department of General and Visceral Surgery, Municipal Hospital Lüneburg, Lüneburg, Germany
- 8 Department of General and Visceral Surgery, Klinikum Osnabrück, Osnabrück, Germany
- 9 Department of General and Visceral Surgery, Evangelisches Krankenhaus Düsseldorf, Düsseldorf, Germany
- 10 Department of General and Visceral Surgery, KMG Klinikum Güstrow, Güstrow, Germany
- 11 Department of General and Visceral Surgery, Klinikum Neumarkt, Neumarkt, Germany
- 12 Department of General and Visceral Surgery, Alfried Krupp Krankenhaus, Essen, Germany
- 13 Department of General and Visceral Surgery, Carl-Thiem-Klinikum Cottbus, Cottbus, Germany
- 14 Department of General and Visceral Surgery, Klinikum Robert Koch Gehrden, Gehrden, Germany
- 15 Department of General and Visceral Surgery, Klinikum Lippe, Detmold, Germany
- 16 Department of General and Visceral Surgery, University Hospital of Jena, Jena, Germany
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Characteristic | Total | SMA-Low | SMA-High | |
---|---|---|---|---|
n (%) | n (%) | n (%) | ||
No. of patients | 321 (100) | 145 (100) | 176 (100) | |
Sex | 0.270 | |||
Male | 157 (48.9) | 66 (45.5) | 91 (51.7) | |
Female | 164 (51.1) | 79 (54.5) | 85 (48.3) | |
Age | 0.996 | |||
<65 | 104 (32.4) | 47 (32.4) | 57 (32.4) | |
≥65 | 217 (67.6) | 98 (67.6) | 119 (67.6) | |
Median follow-up period (months) | 18 | 20 | 16 | |
(range) | (3–98) | (3–72) | (3–98) | |
Preoperative staging | 0.405 | |||
Primarily resectable | 277 (86.3) | 126 (86.9) | 151 (85.8) | |
Borderline resectable | 38 (11.8) | 14 (9.7) | 24 (13.6) | |
Locally advanced | 1 (0.3) | 0 (0.0) | 1 (0.6) | |
Unknown | 5 (1.6) | 5 (3.4) | 0 (0.0) | |
Neoadjuvant therapy | 0.700 | |||
No | 304 (94.7) | 139 (95.9) | 165 (93.8) | |
Chemotherapy | 14 (4.4) | 5 (3.4) | 9 (5.1) | |
Radiochemotherapy | 3 (0.9) | 1 (0.7) | 2 (1.1) | |
pT | 0.870 | |||
1 | 22 (6.9) | 10 (6.9) | 12 (6.8) | |
2 | 121 (37.7) | 52 (35.9) | 69 (39.2) | |
3 | 171 (53.3) | 79 (54.5) | 92 (52.3) | |
4 | 7 (2.2) | 4 (2.8) | 3 (1.7) | |
pN | 0.324 | |||
0 | 93 (29.0) | 46 (31.7) | 47 (26.7) | |
1 | 228 (71.0) | 99 (68.3) | 129 (73.3) | |
R | 0.262 | |||
0 | 207 (64.5) | 88 (60.7) | 119 (67.6) | |
1 | 113 (35.2) | 56 (38.6) | 57 (32.4) | |
2 | 1 (0.3) | 1 (0.7) | 0 (0.0) | |
Pn | 0.340 | |||
0 | 77 (24.0) | 39 (26.9) | 38 (21.6) | |
1 | 232 (72.3) | 103 (71.0) | 129 (73.3) | |
Unknown | 12 (3.7) | 3 (2.1) | 9 (5.1) | |
L | 0.872 | |||
0 | 123 (38.3) | 55 (37.9) | 68 (38.6) | |
1 | 195 (60.8) | 89 (61.4) | 106 (60.2) | |
Unknown | 3 (0.9) | 1 (0.7) | 2 (1.2) | |
V | 0.877 | |||
0 | 221 (68.9) | 99 (68.3) | 122 (69.3) | |
1 | 94 (29.3) | 43 (29.6) | 51 (29.0) | |
Unknown | 6 (1.8) | 3 (2.1) | 3 (1.7) |
Characteristic | Borders | Hazard Ratio | 95% Confidence Interval | p-Value |
---|---|---|---|---|
Preoperative staging | 0.125 | |||
borderline vs. primarily resectable | 1.497 | 0.973–2.304 | 0.066 | |
locally advanced vs. primarily resectable | 2.678 | 0.359–19.988 | 0.337 | |
pT | 0.007 | |||
2 vs. 1 | 1.395 | 0.654–2.976 | 0.389 | |
3 vs. 1 | 2.316 | 1.091–4.916 | 0.029 | |
4 vs. 1 | 1.791 | 0.478–6.717 | 0.387 | |
pN | 1 vs. 0 | 2.177 | 1.449–3.271 | <0.001 |
R | ≥1 vs. 0 | 1.228 | 0.900–1.676 | 0.195 |
Pn | 1 vs. 0 | 0.983 | 0.667–1.449 | 0.931 |
L | 1 vs. 0 | 0.806 | 0.563–1.154 | 0.238 |
V | 1 vs. 0 | 1.064 | 0.750–1.509 | 0.730 |
SMA | high vs. low | 1.389 | 1.019–1.893 | 0.038 |
FAP | high vs. low | 1.249 | 0.921–1.695 | 0.153 |
PDGFR | high vs. low | 1.047 | 0.753–1.455 | 0.786 |
Periostin | high vs. low | 1.078 | 0.790–1.471 | 0.637 |
Characteristic | PeriostinhighSMAlow | PeriostinhighSMAhigh | PeriostinhighSMAlow | PeriostinhighSMAlow | ||
---|---|---|---|---|---|---|
PDGFRlowFAPlow | PDGFRlowFAPhigh | |||||
n (%) | n (%) | n (%) | n (%) | |||
No. of patients | 56 (100.0) | 103 (100.0) | 15 (100.0) | 9 (100.0) | ||
Sex | 0.328 | 0.916 | ||||
Male | 27 (48.2) | 58 (56.3) | 7 (46.7) | 4 (44.4) | ||
Female | 29 (51.8) | 45 (43.7) | 8 (53.3) | 5 (55.6) | ||
Age | 0.411 | 0.562 | ||||
<65 | 21 (37.5) | 32 (31.1) | 5 (33.3) | 2 (22.2) | ||
≥65 | 35 (62.5) | 71 (68.9) | 10 (66.7) | 7 (77.8) | ||
Median follow-up period (months) | 21 | 14 | 31 | 11 | ||
(range) | (3–65) | (4–73) | (6–65) | (4–24) | ||
Preoperative staging | 0.735 | 0.235 | ||||
Primarily resectable | 48 (85.7) | 89 (86.4) | 12 (80.0) | 9 (100.0) | ||
Borderline resectable | 6 (10.7) | 13 (12.6) | 2 (13.3) | 0 (0.0) | ||
Locally advanced | 0 (0.0) | 1 (1.0) | 0 (0.0) | 0 (0.0) | ||
Unknown | 2 (3.6) | 0 (0.0) | 1 (6.7) | 0 (0.0) | ||
Neoadjuvant therapy | 0.101 | - | ||||
No | 56 (100.0) | 95 (92.2) | 15 (100.0) | 9 (100.0) | ||
Chemotherapy | 0 (0.0) | 6 (5.8) | 0 (0.0) | 0 (0.0) | ||
Radiochemotherapy | 0 (0.0) | 2 (1.9) | 0 (0.0) | 0 (0.0) | ||
pT | 0.463 | 0.742 | ||||
1 | 7 (12.5) | 6 (5.8) | 1 (6.7) | 1 (11.1) | ||
2 | 17 (30.4) | 39 (37.9) | 3 (20.0) | 3 (33.3) | ||
3 | 31 (55.4) | 56 (54.4) | 10 (66.7) | 5 (55.6) | ||
4 | 1 (1.8) | 2 (1.9) | 1 (6.7) | 0 (0.0) | ||
pN | 0.749 | 0.572 | ||||
0 | 16 (28.6) | 27 (26.2) | 3 (20.0) | 1 (11.1) | ||
1 | 40 (71.4) | 76 (73.8) | 12 (80.0) | 8 (88.9) | ||
R | 0.218 | 0.729 | ||||
0 | 32 (57.1) | 69 (67.0) | 8 (53.3) | 5 (55.6) | ||
1 | 23 (41.1) | 34 (33.0) | 6 (40.0) | 4 (44.4) | ||
2 | 1 (1.8) | 0 (0.0) | 1 (6.7) | 0 (0.0) | ||
Pn | 0.841 | 0.526 | ||||
0 | 12 (21.4) | 23 (22.3) | 3 (20.0) | 3 (33.3) | ||
1 | 43 (76.8) | 76 (73.8) | 11 (73.3) | 6 (66.7) | ||
Unknown | 1 (1.8) | 4 (3.9) | 1 (6.7) | 0 (0.0) | ||
L | 0.783 | 0.562 | ||||
0 | 24 (42.9) | 41 (39.8) | 5 (33.3) | 2 (22.2) | ||
1 | 32 (57.1) | 60 (58.3) | 10 (66.7) | 7 (77.8) | ||
Unknown | 0 (0.0) | 2 (1.9) | 0 (0.0) | 0 (0.0) | ||
V | 0.487 | 0.285 | ||||
0 | 35 (62.5) | 68 (66.0) | 10 (66.7) | 4 (44.4) | ||
1 | 21 (37.5) | 32 (31.1) | 5 (33.3) | 5 (55.6) | ||
Unknown | 0 (0.0) | 3 (2.9) | 0 (0.0) | 0 (0.0) |
Staining | Treatment-Naïve | Neoadjuvant Treatment | |
---|---|---|---|
n (%) | n (%) | ||
No. of patients | 304 (100.0) | 17 (100.0) | |
FAP | 0.026 | ||
Low | 148 (48.7) | 13 (76.5) | |
High | 156 (51.3) | 4 (23.5) | |
PDGFR | 0.024 | ||
Low | 157 (51.6) | 4 (23.5) | |
High | 147 (48.4) | 13 (76.5) | |
Periostin | 0.813 | ||
Low | 152 (50.0) | 9 (52.9) | |
High | 152 (50.0) | 8 (47.1) | |
SMA | 0.400 | ||
Low | 139 (45.7) | 6 (35.3) | |
High | 165 (54.3) | 11 (64.7) |
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Knipper, K.; Damanakis, A.I.; Zhao, Y.; Bruns, C.J.; Schmidt, T.; Popp, F.C.; Quaas, A.; Lyu, S.I., on behalf of the PANCALYZE Study Group. Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma. Cancers 2023, 15, 2049. https://doi.org/10.3390/cancers15072049
Knipper K, Damanakis AI, Zhao Y, Bruns CJ, Schmidt T, Popp FC, Quaas A, Lyu SI on behalf of the PANCALYZE Study Group. Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma. Cancers. 2023; 15(7):2049. https://doi.org/10.3390/cancers15072049
Chicago/Turabian StyleKnipper, Karl, Alexander I. Damanakis, Yue Zhao, Christiane J. Bruns, Thomas Schmidt, Felix C. Popp, Alexander Quaas, and Su Ir Lyu on behalf of the PANCALYZE Study Group. 2023. "Specific Subtypes of Carcinoma-Associated Fibroblasts Are Correlated with Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma" Cancers 15, no. 7: 2049. https://doi.org/10.3390/cancers15072049