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Table 2 SMAD4 expression in the validation cohort and correlation with clinicopathological patient characteristics (*insignificant after correction for multiple testing)

From: Multiscale heterogeneity in gastric adenocarcinoma evolution is an obstacle to precision medicine

     SMAD4 cytoplasmatic expression SMAD4 nuclear expression
   Total valid Q123 Q4   HScore 0 present HScore 0 absent
   n (%) n (%) n (%) p value n (%) n (%) p value
Total Total 463 (100) 366 (79.1) 97 (20.9)   263 (56.8) 200 (43.2)  
Gender Female 178 (38.4) 144 (80.9) 34 (19.1) 0.482 90 (50.6) 88 (49.4) 0.034
  Male 285 (61.6) 222 (77.9) 63 (22.1)   173 (60.7) 112 (39.3)  
Age group < 68 years 232 (50.1) 190 (81.9) 42 (18.1) 0.139 131 (56.5) 101 (43.5) 0.925
  ≥ 68 years 231 (49.9) 176 (76.2) 55 (23.8)   132 (57.1) 99 (42.9)  
Localization Proximal stomach 145 (31.0) 123 (84.8) 22 (15.2) 0.049 93 (64.1) 52 (35.9) 0.033*
  Distal stomach 318 (69.0) 243 (76.4) 75 (23.6)   170 (53.5) 148 (46.5)  
Laurén phenotype Intestinal 237 (51.2) 186 (78.5) 51 (21.5) 0.313 149 (62.9) 88 (37.1) 0.026
Diffuse 147 (31.7) 122 (83.0) 25 (17.0)   73 (49.7) 74 (50.3)  
  Mixed 31 (6.7) 24 (77.4) 7 (22.6)   19 (61.3) 12 (38.7)  
  Unclassifiable 48 (10.4) 34 (70.8) 14 (29.2)   22 (45.8) 26 (54.2)  
Grading G1 / G2 107 (23.1) 82 (76.6) 25 (23.4) 0.499 62 (57.9) 45 (42.1) 0.824
  G3 / G4 356 (76.9) 284 (79.8) 72 (20.2)   201 (56.5) 155 (43.5)  
pT category T1a / T1b 58 (12.5) 38 (65.5) 20 (34.5) 0.011* 32 (55.2) 26 (44.8) 0.923
  T2 53 (11.4) 38 (71.7) 15 (28.3)   28 (52.8) 25 (47.2)  
  T3 182 (39.3) 150 (82.4) 32 (17.6)   108 (59.3) 74 (40.7)  
  T4a / T4b 170 (36.7) 140 (82.4) 30 (17.6)   95 (55.9) 75 (44.1)  
pN category N0 132 (28.5) 99 (75.0) 33 (25.0) 0.151 69 (52.3) 63 (47.7) 0.399
  N1 63 (13.6) 48 (76.2) 15 (23.8)   39 (61.9) 24 (38.1)  
  N2 85 (18.4) 70 (82.4) 15 (17.6)   49 (57.6) 36 (42.4)  
  N3a/b 182 (39.4) 148 (81.3) 34 (18.7)   106 (58.2) 76 (41.8)  
M category M0 376 (81.2) 291 (77.4) 85 (22.6) 0.079 217 (57.7) 159 (42.3) 0.471
  M1 87 (18.8) 75 (86.2) 12 (13.8)   46 (52.9) 41 (47.1)  
UICC stage IA / IB 79 (17.1) 55 (69.6) 24 (30.4) 0.011* 40 (50.6) 39 (49.4) 0.832
  IIA / IIB 99 (21.4) 77 (77.8) 22 (22.2)   59 (59.6) 40 (40.4)  
  IIIA / IIIB / IIIC 197 (42.6) 158 (80.2) 39 (19.8)   118 (59.9) 79 (40.1)  
  IV 87 (18.8) 75 (86.2) 12 (13.8)   46 (52.9) 41 (47.1)  
Lymph node ratio Low (< 0.189) 226 (48.9) 175 (77.4) 51 (22.6) 0.426 126 (55.8) 100 (44.2) 0.639
High (≥ 0.189) 236 (51.1) 190 (80.5) 46 (19.5)   137 (58.1) 99 (41.9)  
pL category L0 216 (48.8) 167 (77.3) 49 (22.7) 0.645 112 (51.9) 104 (48.1) 0.069
  L1 227 (51.2) 180 (79.3) 47 (20.7)   138 (60.8) 89 (39.2)  
pV category V0 393 (88.9) 308 (78.4) 85 (21.6) 0.856 225 (57.3) 168 (42.7) 0.446
  V1 49 (11.1) 38 (77.6) 11 (22.4)   25 (51.0) 24 (49.0)  
R status R0 400 (87.3) 311 (77.8) 89 (22.3) 0.170 230 (57.5) 170 (42.5) 0.479
  R1 / R2 58 (12.7) 50 (86.2) 8 (13.8)   30 (51.7) 28 (48.3)  
HER2 status Negative 397 (91.9) 320 (80.6) 77 (19.4) 0.657 227 (57.2) 170 (42.8) > 0.999
  Positive 35 (8.1) 27 (77.1) 8 (22.9)   20 (57.1) 15 (42.9)  
H. pylori status Negative 330 (84.6) 261 (79.1) 69 (20.9) 0.092 189 (57.3) 141 (42.7) 0.207
  Positive 60 (15.4) 41 (68.3) 19 (31.7)   29 (48.3) 31 (51.7)  
EBV status Negative 428 (95.5) 341 (79.7) 87 (20.3) 0.273 242 (56.5) 186 (43.5) 0.821
  Positive 20 (4.5) 14 (70.0) 6 (30.0)   12 (60.0) 8 (40.0)  
MSI status MSS 412 (92.2) 332 (80.6) 80 (19.4) 0.008* 236 (57.3) 176 (42.7) 0.375
  MSI 35 (7.8) 21 (60.0) 14 (40.0)   17 (48.6) 18 (51.4)  
p53 status Quartile 1/Quartile 4 226 (49.8) 186 (82.3) 40 (17.7) 0.163 145 (64.2) 81 (35.8) 0.003
  Quartile 2/Quartile 3 228 (50.2) 175 (76.8) 53 (23.2)   115 (50.4) 113 (49.6)  
Overall survival [months] Total / events / censored 451   347 / 289 / 68 94 / 62 / 32 0.001 257 / 210 / 47 194 / 141 / 53 0.035*
Median survival    13.4 ± 1.1 22.4 ± 7.0   14.9 ± 1.4 15.6 ± 1.9  
95% C.I.    11.3–15.5 8.7–36.0   12.2–17.6 12.9–17.1  
Tumor-specific survival [months] Total / events / censored 423   333 / 236 / 97 90 / 51 / 39 0.002 240 / 173 / 67 183 / 114 / 69 0.038*
Median survival    14.7 ± 1.4 30.3 ± 7.5   15.5 ± 1.6 18.4 ± 2.7  
95% C.I.    12.0–17.3 15.5–45.0   12.4–18.5 13.1–23.8