Introduction
Methods
Study design and participants
Factor | Entire cohort (n = 175) n (%) | Esophagus (n = 60) n (%) | GE-junction (n = 45) n (%) | Stomach (n = 66) n (%) |
P*
|
---|---|---|---|---|---|
Age
| |||||
Mean | 70.2 | 76.9 | 69.9 | 72.0 | 0.080 |
Median | 69.8 | 66.02 | 68.7 | 72.6 | |
(Range) | 42.6-94.4 | 48.2-88.5 | 48.7-88.5 | 42.6-94.4 | |
Sex
| |||||
Women | 41 (23.4) | 6 (10.0) | 12 (26.7) | 20 (30.3) | 0.007 |
Men | 134 (76.6) | 54 (90.0) | 33 (73.3) | 46 (69.7) | |
T stage
| |||||
1 | 19 (11.0) | 9 (15.3) | 3 (6.8) | 6 (9.2) | 0.265 |
2 | 32 (18.6) | 10 (16.9) | 4 (9.1) | 17 (26.2) | |
3 | 94 (54.7) | 34 (57.6) | 33 (75.0) | 26 (40.0) | |
4 | 27 (15.7) | 6 (10.2) | 4 (9.1) | 16 (24.6) | |
Missing | 3 | 1 | 1 | 1 | |
Resection margins
| |||||
R0 | 122 (69.7) | 38 (63.3) | 30 (66.7) | 51 (77.3) | 0.016 |
R1 | 34 (19.4) | 10 (16.7) | 11 (24.4) | 12 (18.2) | |
R2 | 19 (10.9) | 12 (20.0) | 4 (8.9) | 3 (4.5) | |
Examined nodes
| |||||
Mean | 29.0 | 36.6 | 29.7 | 25.8 | <0.001 |
Median | 30.2 | 33.5 | 28.00 | 23.0 | |
Range | 1-112 | 10-72 | 8-48 | 1-112 | |
Missing | 14 | 2 | 1 | 11 | |
N stage
| |||||
0 | 59 (33.7) | 15 (25.0) | 12 (26.7) | 28 (42.4) | 0.032 |
1 | 30 (17.1) | 11 (18.3) | 7 (15.6) | 12 (18.2) | |
2 | 41 (23.4) | 15 (25.0) | 14 (31.1) | 12 (18.2) | |
3 | 45 (25.7) | 19 (31.7) | 12 (26.7) | 14 (21.2) | |
M stage
| |||||
0 | 137 (88.4) | 51 (86.4) | 40 (88.9) | 45 (91.8) | 0.377 |
1 | 18 (11.6) | 8 (13.6) | 5 (11.1) | 4 (8.2) | |
Missing | 20 | 1 | 19 | ||
Differentiation grade
| |||||
High | 6 (4.0) | 3 (5.9) | 1 (2.5) | 1 (1.8) | 0.002 |
Intermediate | 40 (26.8) | 21 (41.2) | 9 (22.5) | 9 (16.4) | |
Low | 103 (69.1) | 27 (52.9) | 30 (75.0) | 45 (81.8) | |
Missing | 26 | 9 | 5 | 11 | |
Adjuvant radio/chemotherapy
| |||||
No | 150 (85.7)) | 54 (93.1) | 39 (90.7) | 55 (85.9) | 0.196 |
RT | 1 (0.6) | 1 | 0 | 0 | |
CT with oxaliplatin | 2 (1.1) | 0 | 0 | 2 (3.1) | |
CT without oxaliplatin | 3 (1.7) | 0 | 2 (4.7) | 1 (1.6) | |
RT + CT without oxaliplatin | 6 (3.4) | 2 (3.4) | 2 (4.7) | 2 (3.1) | |
RT + CT, NOS | 2 | 0 | 0 | 2 (3.1) | |
Yes, NOS | 3 (1.7) | 1 (1.7) | 0 | 2 (3.1) | |
Unknown | 8 | 2 | 2 | 2 | |
Location
| |||||
Esophagus | 60 (35.1) | - | - | - | |
GE-junction | 45 (26.3) | - | - | - | |
Stomach | 66 (38.6) | - | - | - | |
Unknown | 4 | ||||
Follow-up
| |||||
Mean | 2.92 | 2.97 | 2.87 | 2.92 | 0.848 |
Median | 2.27 | 2.65 | 2.17 | 2.15 | |
Range | 0.01-7.70 | 0.26-7.70 | 0.01-7.64 | 0.03-7.60 | |
Vital status
| |||||
Alive | 64 (36.6) | 27 (45.0) | 14 (31.1) | 22 (33.3) | 0.184 |
Dead | 111 (63.4) | 33 (55.0) | 31 (68.9) | 44 (66.7) | |
Recurrence
| |||||
No | 64 (46.4) | 24 (46.2) | 14 (38.9) | 25 (50.0) | 0.705 |
Yes | 74 (53.6) | 28 (53.8) | 22 (61.1) | 25 (50.0) | |
Unknown | 37 | 8 | 9 | 16 |
Tissue microarray construction
Immunohistochemistry and staining evaluation
Statistical analysis
Results
PIGR expression in normal tissues, intestinal metaplasia, primary tumours and lymph node metastases
Associations of PIGR expression with clinicopathological characteristics
Factor | Entire cohort median (range) |
p-value
| Esophagus median (range) |
p-value
| GE-junction median (range) |
p-value
| Stomach median (range) |
p-value
|
---|---|---|---|---|---|---|---|---|
Age
| ||||||||
≤ average | 0.610(0.00-3.00) | 0.347 | 1.059(0.00-3.00) | 0.217 | 0.010(0.00-2.75) | 0.034 | 1.250(0.00-3.00) | 0.538 |
>average | 0.605(0.00-3.00) | 0.120(0.00-3.00) | 1.200(0.00-3.00) | 0.987(0.00-3.00) | ||||
Gender
| ||||||||
Female | 0.375(0.00-3.00) | 0.817 | 0.275(0.00-2.85) | 0.816 | 0.330(0.00-3.00) | 0.570 | 0.762(0.00-3.00) | 0.915 |
Male | 0.810(0.00-3.00) | 0.375(0.00-3.00) | 0.342(0.00-3.00) | 1.225(0.00-3.00) | ||||
T-stage
| ||||||||
T1 | 1.930(0.00-3.00) | 0.002 | 2.031(0.12-2.70) | 0.006 | 1.610(1.60-1.96) | 0.154 | 1.970(0.80-3.00) | 0.157 |
T2 | 1.100(0.00-3.00) | 1.150(0.00-3.00) | 0.225(0.00-2.20) | 1.250(0.00-3.00) | ||||
T3 | 0.200(0.00-3.00) | 0.062(0.00-2.85) | 0.342(0.00-3.00) | 0.370(0.00-3.00) | ||||
T4 | 0.128(0.00-3.00) | 0.050(0.00-2.18) | 0.000(0.00-1.06) | 0.717(0.00-3.00) | ||||
N-stage
| ||||||||
N0 | 1.200(0.00-3.00) | 0.193 | 1.560(0.00-2.70) | 0.065 | 1.361(0.00-3.00) | 0.221 | 1.150(0.00-3.00) | 0.043 |
N1 | 0.120(0.00-3.00) | 0.040(0.00-3.00) | 1.610(0.00-2.75) | 0.023(0.00-2.03) | ||||
N2 | 0.375(0.00-3.00) | 0.375(0.00-3.00) | 0.017(0.00-3.00) | 1.021(0.00-3.00) | ||||
N3 | 0.500(0.00-3.00) | 0.100(0.00-1.60) | 0.135(0.00-2.32) | 2.325(0.00-3.00) | ||||
M-stage
| ||||||||
M0 | 0.658(0.00-3.00) | 0.633 | 0.312(0.00-3.00) | 0.828 | 0.570(0.00-3.00) | 0.493 | 1.150(0.00-3.00) | 0.609 |
M1 | 0.238(0.00-3.00) | 0.460(0.00-2.00) | 0.020(0.00-2.32) | 2.05(0.02-2.85) | ||||
Differentiation grade
| ||||||||
High-moderate | 0.671(0.00-3.00) | 0.986 | 1.026(0.00-2.85) | 0.579 | 0.756(0.00-3.00) | 0.307 | 0.600(0.00-3.00) | 0.480 |
Low | 0.605(0.00-3.00) | 0.140(0.00-3.00) | 0.122(0.00-3.00) | 1.262(0.00-3.00) | ||||
Resection margin
| ||||||||
R0 | 1.032(0.00-3.00) | 0.034 | 1.020(0.00-3.00) | 0.249 | 1.069(0.00-3.00) | 0.236 | 1.237(0.00-3.00) | 0.282 |
R1 | 0.010((0.00-3.00) | 0.000(0.00-2.18 | 0.000(0.00-3.00) | 0.022(0.00-3.00) | ||||
R2 | 0.690(0.00-2.85) | 0.660(0.00-2.85) | 0.970(0.00-2.18) | 0.125(0.03-1.80) | ||||
Location
| ||||||||
Esophagus | 0.375(0.00-3.00) | 0.094 | - | - | - | |||
GE-junction | 0.342(0.00-3.00) | - | - | - | ||||
Stomach | 1.150(0.00-3.00) | - | - | - |
Prognostic significance of PIGR expression
Entire cohort | R0 resection | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
n (events) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | n (events) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | |
Age
| ||||||||||
Continuous | 173 | 1.03 (1.01-1.05) | <0.001 | 1.04 (1.03-1.06) | <0.001 | 120 (65) | 1.05 (1.02-1.07) | <0.001 | 1.07 (1.04-1.09) | <0.001 |
Gender
| ||||||||||
Female | 41 (29) | 1.00 | 1.00 | 26 (15) | 1.00 | 1.00 | ||||
Male | 132 (82) | 0.75 (0.49-1.14) | 0.177 | 1.16 (0.11-1.90) | 0.544 | 94 (50) | 0.85 (0.48-1.52) | 0.584 | 1.05 (0.57-1.94) | 0.882 |
T-stage
| ||||||||||
T1 | 18 (5) | 1.00 | 1.00 | 18 (5) | 1.00 | 1.00 | ||||
T2 | 32 (17) | 2.30 (0.85-6.25) | 0.102 | 1.36 (0.47-3.88) | 0.568 | 31 (17) | 2.43 (0.89-6.60) | 0.082 | 1.39 (0.46-4.26) | 0.560 |
T3 | 93 (66) | 3.79 (1.52-9.44) | 0.004 | 1.43 (0.51-3.96) | 0.495 | 55 (34) | 2.94 (1.15-7.53) | 0.025 | 1.23 (0.40-3.72) | 0.716 |
T4 | 27 (21) | 5.59 (2.09-14.90) | 0.001 | 2.12 (0.72-6.28) | 0.175 | 15 (9) | 3.34 (1.11-9.99) | 0.031 | 1.30 (0.34-4.96) | 0.697 |
N-stage
| ||||||||||
N0 | 58 (27) | 1.00 | 1.00 | 46 (18) | 1.00 | 1.00 | ||||
N1 | 29 (17) | 1.41 (0.77-2.59) | 0.266 | 1.61 (0.86-2.98) | 0.133 | 22 (11) | 1.40 (0.66-2.97) | 0.380 | 1.95 (0.90-4.21) | 0.089 |
N2 | 41 (30) | 2.06 (1.22-3.47) | 0.007 | 2.28 (1.32-3.93) | 0.003 | 27 (17) | 2.03 (1.04-3.94) | 0.037 | 3.02 (1.51-6.05) | 0.002 |
N3 | 45 (37) | 3.22 (1.94-5.33) | <0.001 | 3.14 (1.81-5.45) | <0.001 | 25 (19) | 3.45 (1.80-6.64) | <0.001 | 4.95 (2.46-9.93) | <0.001 |
M-stage
| ||||||||||
M0 | 136 (83) | 1.00 | 1.00 | 97 (50) | 1.00 | 1.00 | ||||
M1 | 18 (16) | 2.23 (1.30-3.82) | 0.004 | 1.69 (0.95-3.00) | 0.072 | 10 (9) | 2.78 (1.36-5.67) | 0.005 | 1.54 (0.67-3.53) | 0.311 |
Differentiation
| ||||||||||
High-moderate | 46 (26) | 1.00 | 1.00 | 37 (19) | 1.00 | 1.00 | ||||
Low | 102 (75) | 1.50 (0.96-2.34) | 0.077 | 1.36 (0.85-2.17) | 0.204 | 65 (40) | 1.23 (0.71-2.12) | 0.466 | 1.42 (0.81-2.49) | 0.226 |
Margins
| ||||||||||
R0 | 123 (68) | 1.00 | 1.00 | 1.00 | 1.00 | |||||
R1 | 31 (27) | 2.75 (1.76-4.30) | <0.001 | 2.15 (1.34-3.46) | 0.002 | - | - | |||
R2 | 19 (16) | 2.34 (1.35-4.07) | 0.003 | 2.31 (1.30-4.11) | 0.004 | - | - | |||
Location
| ||||||||||
Esophagus | 59 (33) | 1.00 | 1.00 | 37 (16) | 1.00 | 1.00 | ||||
GE-junction | 45 (31) | 1.32 (0.81-2.16) | 0.266 | 1.51 (0.90-2.56) | 0.120 | 30 (18) | 1.44 (0.74-2.83) | 0.286 | 1.26 (0.62-2.58) | 0.523 |
Stomach | 65 (44) | 1.26 (0.80-1.94) | 0.311 | 1.59 (0.96-2.63) | 0.069 | 50 (29) | 1.44 (0.78-2.66) | 0.237 | 1.41 (0.63-3.16) | 0.409 |
PIGR expression
| ||||||||||
Low | 92 (66) | 1.00 | 1.00 | 37 (58) | 1.00 | 1.00 | ||||
High | 81 (45) | 0.69 (0.47-1.01) | 0.056 | 1.00 (0.66-1.52) | 0.992 | 28 (62) | 0.58 (0.36-0.96) | 0.032 | 0.60 (0.36-0.99) | 0.044 |
R0 resection | R0 resection + M0 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
n (events) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | n (events) | Unadjusted HR (95% CI) | p-value | Adjusted HR (95% CI) | p-value | |
Age
| ||||||||||
Continuous | 105 (46) | 1.00 (0.98-1.03) | 0.728 | 1.04 (1.01-1.08) | 0.005 | 87 (35) | 1.00 (0.97-1.03) | 0.887 | 1.04 (1.00-1.07) | 0.049 |
Gender
| ||||||||||
Female | 20 (5) | 1.00 | 1.00 | 16 (3) | 1.00 | 1.00 | ||||
Male | 85 (41) | 2.04 (0.81-5.18) | 0.132 | 1.97 (0.73-5.36) | 0.183 | 71 (32) | 2.78 (0.85-9.07) | 0.091 | 4.43 (1.21-16.24) | 0.025 |
T-stage
| ||||||||||
T1 | 16 (3) | 1.00 | 1.00 | 11 (1) | 1.00 | 1.00 | ||||
T2 | 28 (10) | 2.32 (0.64-8.44) | 0.201 | 1.78 (0.41-7.75) | 0.440 | 24 (7) | 3.66 (0.45-29.73) | 0.225 | 2.45 (0.26-22.66) | 0.430 |
T3 | 48 (25) | 3.71 (1.12-12.34) | 0.032 | 1.90 (0.46-7.72) | 0.372 | 43 (22) | 7.21 (0.97-53.55) | 0.053 | 3.07 (0.36-26.02) | 0.304 |
T4 | 12 (8) | 6.50 (1.71-24.70) | 0.006 | 2.07 (0.42-10.26) | 0.372 | 8 (5) | 11.29 (1.31-97.00) | 0.027 | 4.50 (0.39-51.49) | 0.226 |
N-stage
| ||||||||||
N0 | 41 (3) | 1.00 | 1.00 | 37 (3) | 1.00 | 1.00 | ||||
N1 | 19 (11) | 10.52 (2.92-37.85) | <0.001 | 13.86 (3.72-51.70) | <0.001 | 17 (10) | 9.31 (2.56-33.87) | 0.001 | 10.11 (2.61-39.22) | 0.001 |
N2 | 26 (16) | 12.97 (3.77-44.67) | <0.001 | 15.68 (4.44-55.41) | <0.001 | 22 (3) | 11.22 (3.19-39.52) | <0.001 | 14.68 (3.85-55.92) | <0.001 |
N3 | 19 (16) | 23.32 (6.75-80.56) | <0.001 | 30.25 (8.48-107.93) | <0.001 | 11 (9) | 19.22 (5.13-71.98) | <0.001 | 46.878 (10.56-208.038) | <0.001 |
M-stage
| ||||||||||
M0 | 87 (35) | 1.00 | 1.00 | - | - | |||||
M1 | 7 (6) | 4.17 (1.74-10.01) | 0.001 | 2.26 (0.77-6.69) | 0.139 | - | - | |||
Differentiation
| ||||||||||
High-moderate | 32 (9) | 1.00 | 1.00 | 31 (9) | 1.00 | 1.00 | ||||
Low | 55 (31) | 2.31 (1.10-4.86) | 0.027 | 2.59 (1.20-5.61) | 0.016 | 39 (20) | 1.91 (0.87-4.19) | 0.108 | 1.20 (0.43-3.34) | 0.727 |
Location
| ||||||||||
Esophagus | 32 (12) | 26 (8) | 1.00 | |||||||
GE-junction | 27 (15) | 1.81 (0.84-3.89) | 0.128 | 1.92 (0.80-4.64) | 0.144 | 25 (13) | 2.00 (1.83-0.83-4.84) | 0.122 | 3.22 (1.19-8.75) | 0.022 |
Stomach | 44 (19) | 1.29 (0.63-2.67) | 0.484 | 1.67 (0.66-4.26) | 0.282 | 35 (14) | 1.49 (0.63-3.56) | 0.367 | 3.86 (1.35-11.03) | 0.011 |
PIGR expression
| ||||||||||
Low | 41 (25) | 1.00 | 1.00 | 33 (21) | 1.00 | 1.00 | ||||
High | 64 (21) | 0.49 (0.27-0.88) | 0.017 | 0.49 (0.27-0.90) | 0.021 | 54 (14) | 0.37 (0.19-0.72) | 0.004 | 0.32 (0.15-0.69) | 0.004 |