Introduction
Materials and methods
Ethics approval
Patients’ characteristics
Immunohistochemical analysis
Methods of evaluation
Statistical analysis
Results
Study population
(A) Feature | N | MST1 | MST2 | LATS1 | LATS2 | pLATS | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
103 | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | |
Gender | ||||||||||||||||||||||||||
Female | 51 | 13 | 14 | 17 | 7 | 0.68 | 8 | 8 | 26 | 9 | 0.82 | 4 | 18 | 20 | 9 | 0.27 | 17 | 13 | 19 | 2 | 0.22 | 15 | 12 | 18 | 6 | 0.61 |
Male | 52 | 16 | 12 | 20 | 4 | 8 | 12 | 24 | 8 | 7 | 19 | 12 | 14 | 18 | 9 | 17 | 8 | 21 | 9 | 18 | 4 | |||||
Neoadjuvant chemotherapy | ||||||||||||||||||||||||||
No | 95 | 26 | 23 | 35 | 11 | 0.17 | 14 | 17 | 47 | 17 | 0.35 | 11 | 35 | 39 | 20 | 0.75 | 33 | 22 | 33 | 7 | 0.06 | 31 | 20 | 34 | 10 | 0.18 |
Yes | 8 | 3 | 3 | 2 | 0 | 2 | 3 | 3 | 0 | 0 | 2 | 3 | 3 | 2 | 0 | 3 | 3 | 5 | 1 | 2 | 0 | |||||
Type of resection | ||||||||||||||||||||||||||
PPDP | 70 | 17 | 18 | 26 | 9 | 0.39 | 13 | 12 | 34 | 11 | 0.89 | 8 | 23 | 26 | 13 | 0.41 | 24 | 18 | 25 | 3 | < 0.01 | 24 | 17 | 25 | 4 | 0.23 |
Left-sided resection | 18 | 9 | 4 | 4 | 1 | 2 | 4 | 9 | 3 | 2 | 6 | 4 | 6 | 4 | 1 | 7 | 6 | 8 | 2 | 6 | 2 | |||||
Total pancreatectomy | 15 | 3 | 4 | 7 | 1 | 1 | 4 | 7 | 3 | 1 | 8 | 2 | 4 | 7 | 3 | 4 | 1 | 4 | 2 | 5 | 4 | |||||
Tumour pathological stage | ||||||||||||||||||||||||||
T1 | 8 | 4 | 0 | 4 | 0 | 0.55 | 0 | 3 | 2 | 3 | 0.35 | 0 | 3 | 4 | 1 | 0.47 | 4 | 0 | 3 | 1 | 0.33 | 2 | 0 | 4 | 2 | 0.11 |
T2 | 12 | 3 | 3 | 4 | 2 | 1 | 3 | 7 | 1 | 1 | 4 | 4 | 3 | 5 | 1 | 6 | 0 | 6 | 2 | 3 | 1 | |||||
T3 | 70 | 19 | 19 | 23 | 9 | 14 | 11 | 33 | 12 | 8 | 23 | 24 | 15 | 19 | 18 | 25 | 8 | 25 | 18 | 20 | 7 | |||||
T4 | 13 | 3 | 4 | 6 | 0 | 1 | 3 | 8 | 1 | 2 | 7 | 0 | 37 | 7 | 3 | 2 | 1 | 3 | 1 | 9 | 0 | |||||
Nodal status | ||||||||||||||||||||||||||
N0 | 25 | 6 | 8 | 8 | 3 | 0.34 | 3 | 3 | 13 | 6 | 0.31 | 2 | 12 | 7 | 4 | 0.09 | 10 | 4 | 8 | 3 | 0.24 | 5 | 4 | 9 | 7 | < 0.01 |
N1 | 70 | 18 | 16 | 28 | 8 | 12 | 13 | 35 | 10 | 8 | 25 | 23 | 14 | 23 | 18 | 22 | 7 | 24 | 17 | 26 | 3 | |||||
N2 | 8 | 5 | 2 | 1 | 0 | 1 | 4 | 2 | 1 | 1 | 0 | 2 | 5 | 2 | 0 | 6 | 0 | 7 | 0 | 1 | 0 | |||||
Metastatic status | ||||||||||||||||||||||||||
M0 | 61 | 4 | 11 | 35 | 11 | < 0.01 | 3 | 5 | 37 | 16 | < 0.01 | 11 | 34 | 13 | 3 | < 0.01 | 32 | 18 | 10 | 1 | < 0.01 | 2 | 14 | 35 | 10 | < 0.01 |
M1 | 42 | 25 | 15 | 2 | 0 | 13 | 15 | 13 | 1 | 0 | 3 | 19 | 20 | 3 | 4 | 26 | 9 | 34 | 7 | 1 | 0 | |||||
Tumour differentiation | ||||||||||||||||||||||||||
Well-differentiated | 7 | 2 | 0 | 3 | 2 | 0.13 | 0 | 1 | 5 | 1 | 0.89 | 1 | 4 | 2 | 0 | 0.21 | 5 | 1 | 1 | 0 | 0.42 | 1 | 3 | 2 | 1 | 0.02 |
Moderately differentiated | 24 | 5 | 6 | 11 | 2 | 4 | 3 | 14 | 3 | 0 | 11 | 7 | 6 | 7 | 8 | 7 | 2 | 4 | 10 | 7 | 3 | |||||
Poorly differentiated | 67 | 21 | 16 | 23 | 7 | 11 | 15 | 29 | 12 | 9 | 22 | 22 | 14 | 22 | 12 | 25 | 8 | 30 | 6 | 26 | 5 | |||||
Anaplastic | 5 | 1 | 4 | 0 | 0 | 1 | 1 | 2 | 1 | 1 | 0 | 1 | 3 | 1 | 1 | 3 | 0 | 1 | 2 | 1 | 1 | |||||
Lymphatic invasion | ||||||||||||||||||||||||||
L0 | 42 | 7 | 11 | 20 | 4 | 0.11 | 5 | 6 | 19 | 12 | 0.04 | 4 | 18 | 15 | 5 | 0.17 | 15 | 13 | 10 | 4 | 0.13 | 9 | 9 | 15 | 9 | < 0.01 |
L1 | 61 | 22 | 15 | 17 | 7 | 11 | 14 | 31 | 5 | 7 | 19 | 17 | 18 | 20 | 9 | 26 | 6 | 27 | 12 | 21 | 1 | |||||
Perineural invasion | ||||||||||||||||||||||||||
Pn0 | 10 | 3 | 1 | 5 | 1 | 0.65 | 1 | 1 | 6 | 2 | 0.78 | 1 | 5 | 2 | 2 | 0.78 | 5 | 3 | 1 | 1 | 0.36 | 2 | 3 | 3 | 2 | 0.48 |
Pn1 | 93 | 26 | 25 | 32 | 10 | 15 | 19 | 44 | 15 | 10 | 32 | 30 | 21 | 30 | 19 | 35 | 9 | 34 | 18 | 33 | 8 | |||||
Venous invasion | ||||||||||||||||||||||||||
V0 | 50 | 14 | 12 | 19 | 5 | 0.97 | 7 | 8 | 27 | 8 | 0.72 | 5 | 19 | 17 | 9 | 0.74 | 18 | 13 | 12 | 7 | 0.09 | 14 | 11 | 22 | 3 | 0.16 |
V1 | 53 | 15 | 14 | 18 | 6 | 9 | 12 | 23 | 9 | 6 | 18 | 15 | 14 | 17 | 9 | 24 | 3 | 22 | 10 | 14 | 7 | |||||
Resection margin | ||||||||||||||||||||||||||
R0 | 68 | 15 | 18 | 26 | 9 | 0.23 | 12 | 6 | 36 | 14 | < 0.01 | 8 | 27 | 22 | 11 | 0.21 | 29 | 17 | 16 | 6 | < 0.01 | 13 | 18 | 28 | 9 | < 0.01 |
R1 | 35 | 14 | 8 | 11 | 2 | 4 | 14 | 14 | 3 | 3 | 10 | 10 | 12 | 6 | 5 | 20 | 4 | 23 | 3 | 8 | 1 | |||||
Tumour size [cm]a, median ± SMD: 3.5 ± 1.47 | ||||||||||||||||||||||||||
≤ 3.5 | 49 | 16 | 8 | 16 | 9 | 0.12 | 5 | 4 | 28 | 12 | < 0.01 | 6 | 15 | 19 | 9 | 0.14 | 20 | 8 | 16 | 5 | 0.58 | 14 | 13 | 19 | 3 | 0.14 |
> 3.5 | 34 | 10 | 10 | 13 | 1 | 3 | 13 | 15 | 3 | 3 | 14 | 6 | 11 | 9 | 8 | 13 | 4 | 16 | 3 | 12 | 3 | |||||
Tumour localization | ||||||||||||||||||||||||||
Head | 81 | 18 | 20 | 32 | 11 | 0.21 | 13 | 16 | 37 | 15 | 0.81 | 10 | 29 | 27 | 15 | 0.45 | 30 | 20 | 28 | 3 | < 0.01 | 26 | 19 | 29 | 7 | 0.36 |
Body | 7 | 3 | 1 | 3 | 0 | 1 | 1 | 4 | 1 | 0 | 3 | 2 | 2 | 3 | 0 | 3 | 1 | 4 | 0 | 3 | 0 | |||||
Tail | 11 | 6 | 3 | 2 | 0 | 2 | 1 | 7 | 1 | 1 | 4 | 3 | 3 | 2 | 1 | 5 | 3 | 3 | 2 | 4 | 2 | |||||
Body + tail | 4 | 2 | 2 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 3 | 0 | 1 | 0 | 3 | 3 | 0 | 0 | 1 |
(B) Feature | N | pYAP | YAP | 14–3-3 | TEAD1 | TEAD2 | TEAD3 | TEAD4 | ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
103 | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | 0 | 1 | 2 | 3 | p | |
Gender | ||||||||||||||||||||||||||||||||||||
Female | 51 | 15 | 8 | 15 | 13 | 0.61 | 16 | 13 | 17 | 5 | 0.49 | 11 | 7 | 28 | 5 | 0.31 | 16 | 21 | 13 | 0 | 0.58 | 15 | 15 | 13 | 8 | 0.29 | 15 | 11 | 24 | 1 | 0.26 | 17 | 20 | 13 | 1 | 0.47 |
Male | 52 | 21 | 5 | 15 | 11 | 15 | 9 | 18 | 10 | 15 | 11 | 19 | 7 | 21 | 17 | 14 | 1 | 22 | 13 | 14 | 3 | 18 | 14 | 16 | 4 | 17 | 14 | 20 | 1 | |||||||
Neoadjuvant chemotherapy | ||||||||||||||||||||||||||||||||||||
No | 95 | 30 | 12 | 30 | 23 | 0.07 | 29 | 21 | 34 | 11 | 0.04 | 21 | 17 | 46 | 11 | 0.11 | 32 | 37 | 25 | 1 | 0.46 | 37 | 25 | 24 | 9 | 0.18 | 31 | 23 | 37 | 4 | 0.76 | 33 | 31 | 30 | 1 | 0.15 |
Yes | 8 | 6 | 1 | 0 | 1 | 2 | 1 | 1 | 4 | 5 | 1 | 1 | 1 | 5 | 1 | 2 | 0 | 0 | 3 | 3 | 2 | 2 | 2 | 3 | 1 | 1 | 3 | 3 | 1 | |||||||
Type of resection | ||||||||||||||||||||||||||||||||||||
PPDP | 70 | 22 | 10 | 21 | 17 | 0.47 | 20 | 14 | 24 | 12 | 0.59 | 16 | 10 | 34 | 10 | 0.32 | 20 | 29 | 20 | 1 | 0.43 | 27 | 19 | 20 | 4 | 0.29 | 27 | 17 | 24 | 2 | 0.14 | 24 | 22 | 23 | 1 | 0.28 |
Left-sided resection | 18 | 10 | 2 | 4 | 2 | 4 | 4 | 8 | 2 | 6 | 6 | 6 | 0 | 10 | 4 | 4 | 0 | 4 | 5 | 5 | 4 | 4 | 2 | 10 | 2 | 6 | 4 | 8 | 0 | |||||||
Total pancreatectomy | 15 | 4 | 1 | 5 | 5 | 7 | 4 | 3 | 1 | 4 | 2 | 7 | 2 | 7 | 6 | 3 | 0 | 6 | 4 | 2 | 3 | 2 | 6 | 6 | 1 | 4 | 8 | 2 | 1 | |||||||
Tumour pathological stage | ||||||||||||||||||||||||||||||||||||
T1 | 8 | 2 | 0 | 3 | 3 | 0.51 | 2 | 3 | 1 | 2 | 0.61 | 2 | 3 | 3 | 0 | 0.14 | 3 | 2 | 3 | 0 | 0.85 | 5 | 0 | 2 | 1 | 0.08 | 4 | 2 | 2 | 0 | 0.47 | 2 | 3 | 3 | 0 | 0.75 |
T2 | 12 | 5 | 2 | 2 | 3 | 3 | 3 | 3 | 3 | 4 | 0 | 8 | 0 | 3 | 7 | 2 | 0 | 5 | 5 | 2 | 0 | 3 | 3 | 6 | 0 | 2 | 4 | 6 | 0 | |||||||
T3 | 70 | 27 | 9 | 18 | 16 | 21 | 12 | 28 | 9 | 18 | 14 | 30 | 8 | 26 | 23 | 20 | 1 | 19 | 20 | 23 | 8 | 20 | 15 | 30 | 5 | 25 | 23 | 21 | 1 | |||||||
T4 | 13 | 2 | 2 | 7 | 2 | 5 | 4 | 3 | 1 | 2 | 1 | 6 | 4 | 5 | 6 | 2 | 0 | 8 | 3 | 0 | 2 | 6 | 5 | 2 | 0 | 5 | 4 | 3 | 1 | |||||||
Nodal status | ||||||||||||||||||||||||||||||||||||
N0 | 25 | 8 | 2 | 6 | 9 | 0.09 | 8 | 4 | 8 | 5 | 0.24 | 5 | 3 | 17 | 0 | 0.04 | 6 | 8 | 11 | 0 | 0.23 | 13 | 4 | 5 | 3 | 0.12 | 9 | 5 | 10 | 1 | 0.89 | 4 | 7 | 12 | 2 | 0.03 |
N1 | 70 | 24 | 8 | 24 | 14 | 22 | 15 | 26 | 7 | 17 | 15 | 28 | 10 | 29 | 25 | 15 | 1 | 23 | 22 | 17 | 8 | 21 | 19 | 27 | 3 | 26 | 26 | 18 | 0 | |||||||
N2 | 8 | 4 | 3 | 0 | 1 | 1 | 3 | 1 | 3 | 4 | 0 | 2 | 2 | 2 | 5 | 1 | 0 | 1 | 2 | 5 | 0 | 3 | 1 | 3 | 1 | 4 | 1 | 3 | 0 | |||||||
Metastatic status | ||||||||||||||||||||||||||||||||||||
M0 | 61 | 8 | 3 | 27 | 23 | < 0.01 | 29 | 15 | 13 | 4 | < 0.01 | 3 | 9 | 37 | 12 | < 0.01 | 26 | 23 | 12 | 0 | 0.12 | 31 | 17 | 11 | 2 | < 0.01 | 26 | 19 | 16 | 0 | < 0.01 | 23 | 23 | 14 | 1 | 0.12 |
M1 | 42 | 28 | 10 | 3 | 1 | 2 | 7 | 22 | 11 | 23 | 9 | 10 | 0 | 11 | 15 | 15 | 1 | 6 | 11 | 16 | 9 | 7 | 6 | 24 | 5 | 11 | 11 | 19 | 1 | |||||||
Tumour differentiation | ||||||||||||||||||||||||||||||||||||
Well-differentiated | 7 | 1 | 0 | 3 | 3 | 0.53 | 2 | 1 | 2 | 2 | 0.84 | 1 | 2 | 4 | 0 | 0.64 | 3 | 3 | 1 | 0 | 0.61 | 5 | 1 | 1 | 0 | 0.02 | 5 | 1 | 1 | 0 | 0.34 | 2 | 1 | 3 | 1 | 0.24 |
Moderately differentiated | 24 | 7 | 1 | 9 | 7 | 8 | 6 | 9 | 1 | 4 | 5 | 11 | 4 | 8 | 10 | 5 | 1 | 8 | 6 | 7 | 3 | 10 | 5 | 9 | 0 | 10 | 8 | 6 | 0 | |||||||
Poorly differentiated | 67 | 26 | 11 | 17 | 13 | 19 | 15 | 22 | 11 | 20 | 9 | 31 | 7 | 24 | 22 | 21 | 0 | 24 | 21 | 14 | 8 | 16 | 18 | 28 | 5 | 19 | 23 | 24 | 1 | |||||||
Anaplastic | 5 | 2 | 1 | 1 | 1 | 2 | 0 | 2 | 1 | 1 | 2 | 1 | 1 | 2 | 3 | 0 | 0 | 0 | 0 | 5 | 0 | 2 | 1 | 2 | 0 | 3 | 2 | 0 | 0 | |||||||
Lymphatic invasion | ||||||||||||||||||||||||||||||||||||
L0 | 42 | 8 | 4 | 15 | 15 | 0.01 | 11 | 12 | 10 | 9 | 0.09 | 7 | 7 | 24 | 4 | 0.22 | 13 | 17 | 12 | 0 | 0.67 | 17 | 12 | 8 | 5 | 0.58 | 15 | 10 | 16 | 1 | 0.75 | 10 | 15 | 15 | 2 | 0.16 |
L1 | 61 | 28 | 9 | 15 | 9 | 20 | 10 | 25 | 6 | 19 | 11 | 23 | 8 | 24 | 21 | 15 | 1 | 20 | 16 | 19 | 6 | 18 | 15 | 24 | 4 | 24 | 19 | 18 | 0 | |||||||
Perineural invasion | ||||||||||||||||||||||||||||||||||||
Pn0 | 10 | 2 | 2 | 5 | 1 | 0.29 | 4 | 1 | 1 | 4 | 0.06 | 2 | 1 | 6 | 1 | 0.81 | 3 | 4 | 3 | 0 | 0.96 | 6 | 2 | 2 | 0 | 0.34 | 5 | 3 | 2 | 0 | 0.42 | 4 | 3 | 3 | 0 | 0.94 |
Pn1 | 93 | 34 | 11 | 25 | 23 | 27 | 21 | 34 | 11 | 24 | 17 | 41 | 11 | 34 | 34 | 24 | 1 | 31 | 26 | 25 | 11 | 28 | 22 | 38 | 5 | 30 | 31 | 30 | 2 | |||||||
Venous invasion | ||||||||||||||||||||||||||||||||||||
V0 | 50 | 15 | 4 | 19 | 12 | 0.17 | 16 | 12 | 13 | 9 | 0.39 | 13 | 8 | 26 | 3 | 0.29 | 16 | 20 | 13 | 1 | 0.63 | 20 | 14 | 11 | 5 | 0.76 | 17 | 11 | 20 | 2 | 0.92 | 14 | 14 | 20 | 2 | 0.14 |
V1 | 53 | 21 | 9 | 11 | 12 | 15 | 10 | 22 | 6 | 13 | 10 | 21 | 9 | 21 | 18 | 14 | 0 | 17 | 14 | 16 | 6 | 16 | 14 | 20 | 3 | 20 | 20 | 13 | 0 | |||||||
Resection margin | ||||||||||||||||||||||||||||||||||||
R0 | 68 | 16 | 9 | 23 | 20 | < 0.01 | 24 | 12 | 21 | 11 | 0.26 | 13 | 13 | 34 | 8 | 0.25 | 25 | 25 | 17 | 1 | 0.88 | 28 | 16 | 18 | 6 | 0.37 | 24 | 17 | 24 | 3 | 0.69 | 24 | 20 | 22 | 2 | 0.55 |
R1 | 35 | 20 | 4 | 7 | 4 | 7 | 10 | 14 | 4 | 13 | 5 | 13 | 4 | 12 | 13 | 10 | 0 | 9 | 12 | 9 | 5 | 9 | 8 | 16 | 2 | 10 | 14 | 11 | 0 | |||||||
Tumour size [cm]a, median ± SMD: 3.5 ± 1.47 | ||||||||||||||||||||||||||||||||||||
≤ 3.5 | 49 | 13 | 8 | 14 | 14 | 0.44 | 15 | 10 | 16 | 8 | 0.86 | 11 | 8 | 26 | 4 | 0.11 | 18 | 14 | 17 | 0 | 0.17 | 15 | 16 | 9 | 9 | 0.11 | 13 | 16 | 19 | 1 | 0.25 | 16 | 11 | 20 | 2 | 0.18 |
> 3.5 | 34 | 14 | 3 | 10 | 7 | 9 | 9 | 12 | 4 | 9 | 7 | 10 | 8 | 13 | 15 | 6 | 0 | 11 | 8 | 13 | 2 | 12 | 6 | 13 | 3 | 11 | 14 | 9 | 0 | |||||||
Tumour localization | ||||||||||||||||||||||||||||||||||||
Head | 81 | 24 | 12 | 25 | 20 | 0.23 | 26 | 18 | 25 | 12 | 0.24 | 18 | 12 | 39 | 12 | 0.45 | 23 | 34 | 23 | 1 | 0.26 | 31 | 23 | 21 | 6 | 0.16 | 28 | 23 | 27 | 3 | 0.12 | 27 | 27 | 26 | 1 | 0.09 |
Body | 7 | 3 | 1 | 1 | 2 | 2 | 3 | 1 | 1 | 3 | 1 | 3 | 0 | 4 | 2 | 1 | 0 | 3 | 2 | 0 | 2 | 1 | 2 | 4 | 0 | 1 | 4 | 1 | 1 | |||||||
Tail | 11 | 7 | 0 | 4 | 0 | 3 | 1 | 5 | 2 | 3 | 4 | 4 | 0 | 7 | 1 | 3 | 0 | 2 | 1 | 5 | 3 | 4 | 0 | 6 | 1 | 6 | 2 | 3 | 0 | |||||||
Body + tail | 4 | 2 | 0 | 0 | 2 | 0 | 0 | 4 | 0 | 2 | 1 | 1 | 0 | 3 | 1 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 3 | 1 | 0 | 1 | 3 | 0 |
Expression of kinases MST1/2, LATS1/2 and pLATS
Antibody | PDAC | Healthy pancreatic tissue | p | PDAC | Liver metastasis | p | Liver metastasis | Healthy liver tissue | p |
---|---|---|---|---|---|---|---|---|---|
MST1 | |||||||||
Negative | 29 | 18 | < 0.01 | 17 | 23 | 0.64 | 23 | 5 | 0.33 |
Weak | 26 | 45 | 11 | 3 | 3 | 10 | |||
Mild | 37 | 35 | 1 | 2 | 2 | 8 | |||
Strong | 11 | 5 | 0 | 1 | 1 | 6 | |||
MST2 | |||||||||
Negative | 16 | 13 | < 0.01 | 9 | 16 | 0.08 | 16 | 13 | 0.19 |
Weak | 20 | 20 | 11 | 11 | 11 | 15 | |||
Mild | 50 | 64 | 9 | 1 | 1 | 0 | |||
Strong | 17 | 6 | 0 | 1 | 1 | 1 | |||
LATS1 | |||||||||
Negative | 11 | 1 | < 0.01 | 2 | 1 | 0.89 | 1 | 1 | 0.83 |
Weak | 37 | 34 | 6 | 7 | 7 | 8 | |||
Mild | 32 | 68 | 13 | 15 | 15 | 15 | |||
Strong | 23 | 0 | 8 | 6 | 6 | 5 | |||
LATS2 | |||||||||
Negative | 35 | 7 | 0.12 | 2 | 3 | 0.35 | 3 | 1 | < 0.01 |
Weak | 22 | 38 | 5 | 10 | 10 | 5 | |||
Mild | 36 | 54 | 18 | 15 | 15 | 22 | |||
Strong | 10 | 4 | 4 | 1 | 1 | 1 | |||
pLATS | |||||||||
Negative | 30 | 6 | < 0.01 | 23 | 23 | 0.58 | 23 | 10 | 0.08 |
Weak | 12 | 25 | 6 | 3 | 3 | 7 | |||
Mild | 22 | 35 | 0 | 3 | 3 | 12 | |||
Strong | 10 | 8 | 0 | 0 | 0 | 0 | |||
pYAP | |||||||||
Negative | 36 | 33 | < 0.01 | 18 | 20 | 0.15 | 20 | 18 | 0.72 |
Weak | 13 | 38 | 8 | 7 | 7 | 9 | |||
Mild | 28 | 26 | 2 | 2 | 2 | 2 | |||
Strong | 23 | 3 | 1 | 0 | 0 | 0 | |||
YAP | |||||||||
Negative | 31 | 48 | < 0.01 | 2 | 6 | 0.06 | 6 | 12 | 0.08 |
Weak | 22 | 36 | 6 | 4 | 4 | 6 | |||
Mild | 35 | 19 | 15 | 13 | 13 | 11 | |||
Strong | 15 | 0 | 6 | 6 | 6 | 0 | |||
14-3-3 | |||||||||
Negative | 26 | 18 | < 0.01 | 16 | 21 | 0.58 | 21 | 11 | 0.08 |
Weak | 18 | 27 | 6 | 6 | 6 | 12 | |||
Mild | 47 | 49 | 7 | 2 | 2 | 6 | |||
Strong | 12 | 9 | 0 | 0 | 0 | 0 | |||
TEAD1 | |||||||||
Negative | 37 | 60 | < 0.01 | 4 | 20 | 0.26 | 20 | 27 | < 0.01 |
Weak | 38 | 32 | 9 | 5 | 5 | 2 | |||
Mild | 27 | 11 | 15 | 3 | 3 | 0 | |||
Strong | 1 | 0 | 1 | 1 | 1 | 0 | |||
TEAD2 | |||||||||
Negative | 37 | 45 | < 0.01 | 2 | 5 | 0.67 | 5 | 5 | < 0.01 |
Weak | 28 | 23 | 9 | 6 | 6 | 11 | |||
Mild | 27 | 30 | 11 | 15 | 15 | 12 | |||
Strong | 11 | 5 | 7 | 3 | 3 | 1 | |||
TEAD3 | |||||||||
Negative | 33 | 72 | < 0.01 | 4 | 9 | 0.55 | 9 | 13 | 0.55 |
Weak | 25 | 26 | 5 | 8 | 8 | 12 | |||
Mild | 40 | 5 | 16 | 11 | 11 | 4 | |||
Strong | 5 | 0 | 4 | 1 | 1 | 0 | |||
TEAD4 | |||||||||
Negative | 34 | 76 | 0.02 | 7 | 13 | 0.32 | 13 | 17 | 0.03 |
Weak | 34 | 22 | 7 | 11 | 11 | 10 | |||
Mild | 33 | 5 | 15 | 5 | 5 | 2 | |||
Strong | 2 | 9 | 0 | 0 | 0 | 0 |
Expression of YAP, pYAP and 14-3-3
Expression of transcriptional factors TEAD1-4
Activity of the Hippo pathway as an indicator for post-surgical prognosis
Variable | No. | Median OS [months] | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
Hazard ratio (95% CI) | p value | Hazard ratio (95% CI) | p value | |||
Ratio pYAP/YAP expression | ||||||
pYAP > YAP | 53 | 19.0 | 1.00 | 1.00 | ||
YAP > pYAP | 50 | 13.0 | 1.34 (0.86–2.11) | 0.20 | 1.57 (0.53–4.71) | 0.42 |
YAP expression | ||||||
Negative | 31 | 17.0 | 1.00 | 1.00 | ||
Positive, weak | 22 | 24.0 | 0.66 (0.34–1.28) | 0.22 | 0.34 (0.13–0.89) | 0.78 |
Positive, mild | 35 | 14.0 | 0.89 (0.51–1.56) | 0.69 | 1.19 (0.16–1.54) | 0.12 |
Positive, strong | 15 | 13.0 | 1.01 (0.52–2.20) | 0.84 | 1.03 (0.19–2.43) | 0.49 |
pYAP expression | ||||||
Negative | 36 | 13.0 | 1.00 | 1.00 | ||
Positive, weak | 13 | 9.0 | 1.79 (0.90–3.56) | 0.09 | 1.27 (0.49–3.24) | 0.62 |
Positive, mild | 28 | 25.5 | 0.47 (0.26–0.84) | 0.01 | 0.41 (0.17–0.99) | 0.04 |
Positive, strong | 23 | 21.0 | 0.69 (0.36–1.23) | 0.19 | 1.42 (0.40–4.96) | 0.59 |
Tumour pathological stage | ||||||
T1 | 8 | 19.0 | 1.00 | 1.00 | ||
T2 | 12 | 10.0 | 1.66 (0.39–6.97) | 0.49 | 0.94 (0.19–4.47) | 0.94 |
T3 | 70 | 9.0 | 2.64 (0.83–8.46) | 0.10 | 1.30 (0.37–4.62) | 0.69 |
T4 | 13 | 13.0 | 2.74 (0.75–10.1) | 0.13 | 2.14 (0.56–8.23) | 0.27 |
Nodal status | ||||||
N0 | 25 | 23.0 | 1.00 | 1.00 | ||
N1 | 70 | 16.0 | 1.74 (0.95–3.19) | 0.08 | 1.90 (0.94–3.85) | 0.13 |
N2 | 8 | 9.0 | 2.85 (0.91–8.98) | 0.07 | 3.09 (0.84–11.4) | 0.52 |
Metastasis status | ||||||
M0 | 61 | 20.0 | 1.00 | 1.00 | ||
M1 | 42 | 11.5 | 1.66 (1.05–2.62) | 0.03 | 2.19 (0.71–6.83) | 0.17 |
Tumour differentiation | ||||||
Well-differentiated | 7 | 33.0 | 1.00 | 1.00 | ||
Moderately differentiated | 24 | 20.0 | 2.19 (0.72–6.65) | 0.17 | 2.06 (0.58–7.33) | 0.26 |
Poorly differentiated | 67 | 14.0 | 3.10 (1.10–8.65) | 0.03 | 2.65 (0.84–8.39) | 0.09 |
Anaplastic | 5 | 16.0 | 1.96 (0.43–8.87) | 0.38 | 1.51 (0.28–8.23 | 0.64 |
Resection margin | ||||||
R0 | 68 | 17.0 | 1.00 | 1.00 | ||
R1 | 35 | 14.0 | 1.24 (0.77–2.01) | 0.37 | 1.08 (0.61–1.92) | 0.78 |
Variable | No. | Median DFS [months] | Univariate | Multivariate | ||
---|---|---|---|---|---|---|
Hazard ratio (95% CI) | p value | Hazard ratio (95% CI) | p value | |||
Ratio pYAP/YAP expression | ||||||
pYAP > YAP | 39 | 11.0 | 1.00 | 1.00 | ||
YAP > pYAP | 36 | 9.0 | 1.26 (0.75–2.14) | 0.39 | 3.18 (0.62–16.3) | 0.02 |
YAP expression | ||||||
Negative | 21 | 9.0 | 1.00 | 1.00 | ||
Positive, weak | 17 | 12.0 | 0.77 (0.36–1.65) | 0.49 | 0.57 (0.13–2.50) | 0.45 |
Positive, mild | 24 | 9.5 | 1.01 (0.52–1.98) | 0.97 | 0.93 (0.17–5.24) | 0.94 |
Positive, strong | 13 | 10.0 | 1.71 (0.69–3.09) | 0.12 | 1.92 (0.24–15.3) | 0.04 |
pYAP expression | ||||||
Negative | 24 | 8.5 | 1.00 | 1.00 | ||
Positive, weak | 11 | 5.0 | 1.01 (0.47–2.14) | 0.99 | 0.33 (0.09–1.25) | 0.10 |
Positive, mild | 22 | 18.0 | 0.27 (0.13–0.57) | < 0.01 | 0.10 (0.03–0.35) | < 0.01 |
Positive, strong | 18 | 10.5 | 0.48 (0.24–0.98) | 0.04 | 0.27 (0.04–1.65) | 0.16 |
Tumour pathological stage | ||||||
T1 | 7 | 19.0 | 1.00 | 1.00 | ||
T2 | 11 | 10.0 | 2.69 (0.71–10.2) | 0.14 | 1.83 (0.34–9.75) | 0.48 |
T3 | 50 | 9.0 | 2.62 (0.81–8.50) | 0.11 | 1.72 (0.44–6.70) | 0.44 |
T4 | 7 | 13.0 | 3.83 (0.95–15.4) | 0.06 | 6.08 (1.15–32.3) | 0.03 |
Nodal status | ||||||
N0 | 18 | 18.0 | 1.00 | 1.00 | ||
N1 | 49 | 10.0 | 1.63 (0.81–3.29) | 0.17 | 2.03 (0.87–4.70) | 0.10 |
N2 | 8 | 3.0 | 6.91 (2.60–18.3) | < 0.01 | 9.59 (2.52–36.5) | < 0.01 |
Metastasis status | ||||||
M0 | 44 | 11.0 | 1.00 | 1.00 | ||
M1 | 31 | 9.0 | 1.62 (0.95–2.75) | 0.07 | 1.17 (0.22–6.12) | 0.85 |
Tumour differentiation | ||||||
Well-differentiated | 4 | 32.5 | 1.00 | |||
Moderately differentiated | 18 | 11.5 | 6.31 (0.82–48.5) | 0.07 | 6.92 (0.77–62.1) | 0.08 |
Poorly differentiated | 51 | 9.0 | 7.92 (1.08–58.2) | 0.04 | 7.55 (0.89–64.4) | 0.06 |
Anaplastic | 2 | 22.0 | 3.42 (0.21–55.2) | 0.39 | 9.04 (0.41–200.6) | 0.16 |
Resection margin | ||||||
R0 | 50 | 10.0 | 1.00 | 1.00 | ||
R1 | 25 | 10.0 | 1.09 (0.63–1.91) | 0.74 | 1.77 (0.97–3.23) | 0.08 |