Background
Methods
Data collection
Microarray hybridization
Microarray data analysis
Molecular subtype discovery
Gene filtering
Identification of subclasses using non-negative matrix factorization clustering
Merging microarray data using DWD
Bioinformatic analysis
Survival analysis
Master regulator analysis
HNF1B immunohistochemistry
Results
Gene expression profiling
Molecular subtypes linked to survival
Number of Patients | Disease-free Survival Time (DFS; median (CI): months) | Univariable | Multivariable | ||||
---|---|---|---|---|---|---|---|
Hazard ratio (HR) (95% CI) | p-value | Hazard ratio (HR) (95% CI) | p-value | ||||
Clinicopathological Parameter | |||||||
Age | < 64 y. | 58 | 10.2 (6.4 - 13.3) | 0.756 (0.508 - 1.122) | 0.165 | ||
> 64 y. | 60 | 9.0 (7.3 - 10.9) | |||||
Gender | Female | 53 | 10.9 (8.1 - 13.5) | 0.785 (0.528 - 1.161) | 0.226 | ||
Male | 65 | 7.8 (6.0 - 11.1) | |||||
PDAC Location | Head | 93 | 9.8 (7.4 - 12.4) | 0.564 (0.357 - 0.921) |
0.023
| 0.581 (0.340 - 1.015) | 0.056 |
Body or Tail | 25 | 8.3 (4.4 - 11.1) | |||||
Tumor diameter | < 2 cm | 27 | 13.1 (6.7 - 17.0) | 0.676 (0.411 - 1.064) | 0.092 | 0.739 (0.399 - 1.306) | 0.306 |
> 2 cm | 91 | 7.8 (3.3 - 18.9) | |||||
pG | 1 | 10 | 13.1 (4.0 - 24.3) | 0.715 | |||
2 | 41 | 10.2 (7.1 - 16.2) | |||||
3 | 67 | 7.7 (6.0 - 11.0) | |||||
pT | 1 | 2 | 7.7 (7.3 - 8.1) | 0.857 | |||
2 | 13 | 11.6 (7.1 - 17.1) | |||||
3 | 95 | 9.0 (6.8 - 11.4) | |||||
4 | 8 | 8.4 (7.4 - 11.2) | |||||
pN | 0 | 45 | 10.3 (6.1 - 13.1) | 0.839 (0.557 - 1.248) | 0.39 | ||
1 | 73 | 8.8 (7.3 - 11.4) | |||||
pM | 0 | 105 | 10.0 (7.7 - 12.3) | 0.411 (0.230 - 0.802) |
0.011
| 0.441 (0.097 - 1.458) | 0.19 |
1 | 13 | 4.7 (3.2 - 10.9) | |||||
pR | 0 | 91 | 10.0 (7.8 - 12.4) | 0.712 (0.458 - 1.149) | 0.159 | ||
1 | 27 | 7.7 (7.4 - 11.2) | |||||
pRM | < 1 mm | 64 | 10.0 (6.3 - 13.1) | 0.925 (0.621 - 1.382) | 0.7 | ||
> 1 mm | 50 | 9.8 (7.0 - 12.3) | |||||
PNI | 0 | 15 | 17.1 (3.3 - 56.1) | 0.528 (0.264 - 0.955) |
0.034
| 0.516 (0.233 - 1.053) | 0.07 |
1 | 101 | 9.8 (7.4 - 11.4) | |||||
VI | 0 | 36 | 11.1 (7.0 - 18.9) | 0.629 (0.399 - 0.969) |
0.035
| 0.805 (0.485 - 1.303) | 0.382 |
1 | 76 | 8.0 (6.4 - 11.0) | |||||
LVI | 0 | 34 | 10.2 (6.1 - 14.3) | 0.833 (0.529 - 1.276) | 0.408 | ||
1 | 81 | 8.8 (7.3 - 11.4) | |||||
ECLNI | 0 | 69 | 10.4 (7.3 - 13.3) | 0.821 (0.544 - 1.254) | 0.356 | ||
1 | 43 | 8.4 (6.3 - 11.1) | |||||
AJCC TNM Stage 7th Ed. | ≤ 2a | 38 | 10.9 (6.8 - 14.3) | 0.730 (0.474 - 1.100) | 0.134 | ||
≥ 2b | 80 | 8.5 (7.0 - 11.1) | |||||
N0 <T3 M0 (Early) | 38 | 10.9 (6.8 - 14.3) | Early vs Adv 0.498 (0.273 - 0.950) | Overall 0.104 | Overall | 0.209 | |
N1 <T3 M0 (LNM) | 62 | 9.8 (7.3 - 12.6) | Early vs Adv 0.035 | 0.915 (0.295 - 4.022) | 0.892 | ||
T4 or M1 (Advanced) | 18 | 5 (3.3 - 10.4) | |||||
Adjuvant chemotherapy | 0 | 36 | 7.4 (4.6 - 11.0) | 1.139 (0.733 - 1.728) | 0.553 | ||
1 | 82 | 10.0 (7.7 - 12.6) | |||||
Molecular Subtypes | |||||||
k2 | Cluster 1 | 64 | 11.6 (7.4 - 16.2) | 0.655 (0.440 - 0.976) |
0.035
| 0.252 (0.092 - 0.888) |
0.034
|
Cluster 2 | 54 | 7.8 (6.7 - 10.0) | |||||
k3 | Cluster 1 | 42 | 13.5 (10.9 - 17.1) | Cl1 vs Cl2 0.602 (0.382 - 0.940) | Overall 0.053 | Overall | 0.318 |
Cluster 2 | 50 | 8.0 (7.0 - 10.0) | Cl1 vs Cl3 0.615 (0.363 - 1.066) | Cl1 vs Cl2 0.026 | |||
Cluster 3 | 26 | 4.7 (3.3 - 11.2) | Cl1 vs Cl3 0.082 | ||||
k4 | Cluster 1 | 39 | 13.3 (9.8 - 16.7) | Cl1 vs Cl2 0.670 (0.418 - 1.065) | Overall 0.333 | Overall | 0.751 |
Cluster 2 | 45 | 8.4 (6.7 - 10.0) | Cl1 vs Cl2 0.090 | ||||
Cluster 3 | 7 | 11.0 (4.8 - 17.1) | |||||
Cluster 4 | 27 | 4.7 (3.3 - 11.2) | |||||
k5 | Cluster 1 | 41 | 13.5 (10.9 - 17.0) | Cl1 vs Cl5 0.488 (0.251 - 1.021) | Overall 0.209 | Overall | 0.616 |
Cluster 2 | 35 | 8.4 (7.0 - 10.2) | Cl1 vs Cl5 0.057 | ||||
Cluster 3 | 4 | 9.3 (4.8 - NA) | |||||
Cluster 4 | 26 | 4.7 (3.3 - 11.2) | |||||
Cluster 5 | 12 | 7.5 (4.3 - 11.0) |
Number of patients | Overall survival time (OS; median (CI): months) | Univariable | Multivariable | ||||
---|---|---|---|---|---|---|---|
Hazard ratio (HR) (95% CI) | p-value | Hazard ratio (HR) (95% CI) | p-value | ||||
Clinicopathological parameter | |||||||
Age | < 64 y. | 58 | 23.5 (12.6 - 33.0) | 0.626 (0.422 - 0.924) |
0.018
| 0.551 (0.350 - 0.859) |
0.008
|
> 64 y. | 60 | 13.7 (11.4 - 16.8) | |||||
Gender | Female | 53 | 20.5 (12.9 - 29.3) | 0.865 (0.587 - 1.269) | 0.459 | ||
Male | 65 | 12.6 (11.2 - 20.1) | |||||
PDAC location | Head | 93 | 19.5 (12.6 - 23.5) | 0.600 (0.384 - 0.967) |
0.036
| 0.714 (0.435 - 1.209) | 0.204 |
Body or Tail | 25 | 12.6 (10.0 - 26.4) | |||||
Tumor diameter | < 2 cm | 27 | 20.5 (11.7 - 36.5) | 0.746 (0.459 - 1.165) | 0.204 | ||
> 2 cm | 91 | 14.8 (11.9 - 20.8) | |||||
pG | 1 | 10 | 22.5 (1.5 - 33.2) | 0.89 | |||
2 | 41 | 14.8 (11.2 - 29.3) | |||||
3 | 67 | 15.9 (11.5 - 23.5) | |||||
pT | 1 | 2 | 13.4 (12.3 - 14.6) | 0.694 | |||
2 | 13 | 26.9 (9.4 - 38.8) | |||||
3 | 95 | 15.9 (11.8 - 21.0) | |||||
4 | 8 | 12.4 (1.3 - 33.0) | |||||
pN | 0 | 45 | 21.0 (14.6 - 29.3) | 0.750 (0.499 - 1.111) | 0.154 | ||
1 | 73 | 12.8 (11.7 - 17.8) | |||||
pM | 0 | 105 | 17.8 (12.9 - 23.5) | 0.569 (0.323 - 1.097) | 0.089 | 0.624 (0.166 - 1.928) | 0.427 |
1 | 13 | 11.4 (5.8 - 12.4) | |||||
pR | 0 | 91 | 16.8 (12.9 - 25.6) | 0.733 (0.474 - 1.174) | 0.19 | ||
1 | 27 | 12.4 (7.0 - 23.4) | |||||
pRM | < 1 mm | 64 | 15.4 (11.8 - 25.6) | 1.096 (0.737 - 1.622) | 0.647 | ||
> 1 mm | 50 | 16.7 (12.3 - 23.5) | |||||
PNI | 0 | 15 | 37.8 (10.6 - NA) | 0.468 (0.227 - 0.860) |
0.013
| 0.561 (0.252 - 1.115) | 0.103 |
1 | 101 | 15.9 (12.4 - 20.8) | |||||
VI | 0 | 36 | 19.7 (11.9 - 33.2) | 0.730 (0.466 - 1.115) | 0.148 | ||
1 | 76 | 12.8 (11.5 - 23.4) | |||||
LVI | 0 | 34 | 19.7 (10.6 - 33.0) | 0.877 (0.561 - 1.334) | 0.547 | ||
1 | 81 | 15 (12.3 - 21.7) | |||||
ECLNI | 0 | 69 | 20.1 (12.9 - 30.5) | 0.654 (0.437 - 0.987) |
0.043
| 0.660 (0.398 - 1.089) | 0.104 |
1 | 43 | 12.4 (10.2 - 20.8) | |||||
AJCC TNM Stage 7th Ed. | ≤ 2a | 38 | 23.5 (16.8 - 31.7) | 0.681 (0.443 - 1.023) | 0.065 | 0.672 (0.166 - 2.254) | 0.53 |
≥ 2b | 80 | 12.6 (11.4 - 16.7) | |||||
Early (pN=0,pT≤ 3,pM=0) | 38 | 23.5 (16.8 - 31.7) | Early vs LNM 0.722 (0.463 - 1.106) | Overall 0.105 | |||
pN=1,pT≤ 3,pM=0 | 62 | 14.8 (11.2 - 21.7) | LNM vs Adv 0.736 (0.425 - 1.328) | Early vs LNM 0.136 | |||
Advanced (pT=4 or pM=1) | 18 | 11.7 (6.6 - 12.4) | Early vs Adv 0.532 (0.295 - 0.997) | Early vs Adv 0.049 | |||
Adjuvant chemotherapy | 0 | 36 | 12.1 (7.0 - 16.8) | 1.337 (0.874 - 2.002) | 0.176 | ||
1 | 82 | 19.8 (13.9 - 25.6) | |||||
Molecular subtypes | |||||||
k2 | Cluster 1 | 64 | 20.9 (12.9 - 29.3) | 0.710 (0.482 - 1.048) | 0.081 | 0.247 (0.092 - 0.860) |
0.031
|
Cluster 2 | 54 | 12.7 (11.2 - 16.7) | |||||
k3 | Cluster 1 | 42 | 24.6 (16.8 - 33.2) | Cl1 vs Cl2 0.680 (0.437 - 1.050) | Overall 0.193 | Overall |
0.017
|
Cluster 2 | 50 | 12.7 (11.2 - 16.7) | Cl2 vs Cl3 1.055 (0.641 - 1.788) | Cl1 vs Cl2 0.082 | |||
Cluster 3 | 26 | 11.8 (6.6 - 20.5) | Cl1 vs Cl3 0.717 (0.426 - 1.236) | Cl1 vs Cl3 0.226 | Cl1 vs Cl3 0.209 (0.057 - 0.809) |
0.024
| |
k4 | Cluster 1 | 39 | 23.5 (14.8 - 33.0) | 0.577 | |||
Cluster 2 | 45 | 12.6 (10.6 - 16.7) | |||||
Cluster 3 | 7 | 26.2 (9.3 - 38.8) | |||||
Cluster 4 | 27 | 11.9 (6.6 - 21.0) | |||||
k5 | Cluster 1 | 41 | 23.5 (14.8 - 33.2) | Cl1 vs Cl5 0.398 (0.210 - 0.808) | Overall 0.122 | Overall | 0.271 |
Cluster 2 | 35 | 13.9 (11.4 - 21.7) | Cl2 vs Cl5 0.483 (0.251 - 0.988) | Cl1 vs Cl5 0.012 | |||
Cluster 3 | 4 | 28.9 (9.3 - NA) | Cl3 vs Cl5 0.298 (0.067 - 0.949) | Cl2 vs Cl5 0.046 | |||
Cluster 4 | 26 | 11.8 (6.6 - 20.5) | Cl3 vs Cl5 0.040 | ||||
Cluster 5 | 12 | 10 (6.9 - 16.6) |