Introduction
Materials and methods
Patients
Clinical data of patients
Hematological test
-
NLR = neutrophils/lymphocytes.
-
PLR = platelets/lymphocytes.
-
MLR = monocytes/lymphocytes.
-
dNLR = [neutrophils/ (leukocytes—neutrophils)].
-
NLPR = [Neutrophils/ (lymphocytes × platelets)].
-
SIRI = [(neutrophils × monocytes)/lymphocytes)].
-
AISI = [(neutrophils × monocytes × platelets)/lymphocytes].
-
SII = [(neutrophils x platelets)/lymphocytes)].
Imaging analysis
Histological evaluation
DNA purification and quantification
Immunohistochemistry Validation in Resected Patients
special staining in resected patients
Statistical analysis
Predictive model development and validation
Construction of nomogram
Nomogram performance
Results
Patient characteristics
Characteristics | All cohort (N = 522) | Validation cohort (N = 156) | Training cohort (N = 366) | p |
---|---|---|---|---|
Gender, n (%) | 0.171 | |||
Female | 284 (54.4) | 92 (59.0) | 192 (52.5) | |
Male | 238 (45.6) | 64 (41.0) | 174 (47.5) | |
Hypertension, n (%) | 0.713 | |||
No | 352 (67.4) | 107 (68.6) | 245 (66.9) | |
Yes | 170 (32.6) | 49 (31.4) | 121 (33.1) | |
Diabetes, n (%) | 0.296 | |||
No | 454 (87.0) | 132 (84.6) | 322 (88.0) | |
Yes | 68 (13.0) | 24 (15.4) | 44 (12.0) | |
COPD, n (%) | 0.279 | |||
No | 516 (98.9) | 153 (98.1) | 363 (99.2) | |
Yes | 6 (1.1) | 3 (1.9) | 3 (0.8) | |
Smoking history, n (%) | 0.338 | |||
Non-smoker | 373 (71.5) | 116 (74.4) | 257 (70.2) | |
Smoker | 149 (28.5) | 40 (25.6) | 109 (29.8) | |
Blood type, n (%) | 0.661 | |||
A | 150 (28.7) | 44 (28.2) | 106 (29.0) | |
B | 191 (36.6) | 52 (33.3) | 139 (38.0) | |
AB | 58 (11.1) | 19 (12.2) | 39 (10.7) | |
O | 123 (23.6) | 41 (26.3) | 82 (22.4) | |
ASA, n (%) | 0.859 | |||
1 | 41 (7.9) | 11 (7.1) | 30 (8.2) | |
2 | 460 (88.1) | 138 (88.5) | 322 (88.0) | |
3 | 21 (4.0) | 7 (4.5) | 14 (3.8) | |
Location, n (%) | 0.714 | |||
Centrality | 61 (11.7) | 17 (10.9) | 44 (12.0) | |
Peripherality | 461 (88.3) | 139 (89.1) | 322 (88.0) | |
Shape, n (%) | 0.584 | |||
Regularity | 175 (33.5) | 55 (35.3) | 120 (32.8) | |
Irregularity | 347 (66.5) | 101 (64.7) | 246 (67.2) | |
Spiculation, n (%) | 0.77 | |||
No | 162 (31.0) | 47 (30.1) | 115 (31.4) | |
Yes | 360 (69.0) | 109 (69.9) | 251 (68.6) | |
Cavitation sign, n (%) | 0.333 | |||
No | 412 (78.9) | 119 (76.3) | 293 (80.1) | |
Yes | 110 (21.1) | 37 (23.7) | 73 (19.9) | |
Calcification, n (%) | 0.142 | |||
No | 517 (99.0) | 156 (100.0) | 361 (98.6) | |
Yes | 5 (1.0) | 0 (0.0) | 5 (1.4) | |
Vascular penetration sign, n (%) | 0.802 | |||
No | 140 (26.8) | 43 (27.6) | 97 (26.5) | |
Yes | 382 (73.2) | 113 (72.4) | 269 (73.5) | |
Pleural adhesions, n (%) | 0.723 | |||
No | 190 (36.4) | 55 (35.3) | 135 (36.9) | |
Yes | 332 (63.6) | 101 (64.7) | 231 (63.1) | |
Bronchus sign, n (%) | 0.514 | |||
No | 352 (67.4) | 102 (65.4) | 250 (68.3) | |
Yes | 170 (32.6) | 54 (34.6) | 116 (31.7) | |
Lobulation, n (%) | 0.2 | |||
No | 262 (50.2) | 85 (54.5) | 177 (48.4) | |
Yes | 260 (49.8) | 71 (45.5) | 189 (51.6) | |
Lymph node enlargement sign, n (%) | 0.677 | |||
No | 426 (81.6) | 129 (82.7) | 297 (81.1) | |
Yes | 96 (18.4) | 27 (17.3) | 69 (18.9) | |
Pleural effusion sign, n (%) | 0.853 | |||
No | 516 (98.9) | 154 (98.7) | 362 (98.9) | |
Yes | 6 (1.1) | 2 (1.3) | 4 (1.1) | |
Lepidic, n (%) | 0.362 | |||
No | 162 (31.0) | 44 (28.2) | 118 (32.2) | |
Yes | 360 (69.0) | 112 (71.8) | 248 (67.8) | |
Acinar, n (%) | 0.141 | |||
No | 97 (18.6) | 23 (14.7) | 74 (20.2) | |
Yes | 425 (81.4) | 133 (85.3) | 292 (79.8) | |
Papillary, n (%) | 0.453 | |||
No | 314 (60.2) | 90 (57.7) | 224 (61.2) | |
Yes | 208 (39.8) | 66 (42.3) | 142 (38.8) | |
Micropapillary, n (%) | 0.495 | |||
No | 421 (80.7) | 123 (78.8) | 298 (81.4) | |
Yes | 101 (19.3) | 33 (21.2) | 68 (18.6) | |
Solid, n (%) | 0.862 | |||
No | 490 (93.9) | 146 (93.6) | 344 (94.0) | |
Yes | 32 (6.1) | 10 (6.4) | 22 (6.0) | |
Mucinous, n (%) | 0.642 | |||
No | 446 (85.4) | 135 (86.5) | 311 (85.0) | |
Yes | 76 (14.6) | 21 (13.5) | 55 (15.0) | |
CK5/6, n (%) | 0.098 | |||
No | 496 (95.0) | 152 (97.4) | 344 (94.0) | |
Yes | 26 (5.0) | 4 (2.6) | 22 (6.0) | |
CK7, n (%) | 0.921 | |||
No | 393 (75.3) | 117 (75.0) | 276 (75.4) | |
Yes | 129 (24.7) | 39 (25.0) | 90 (24.6) | |
TTF-1, n (%) | 0.746 | |||
No | 373 (71.5) | 113 (72.4) | 260 (71.0) | |
Yes | 149 (28.5) | 43 (27.6) | 106 (29.0) | |
Napsin A, n (%) | 0.154 | |||
No | 452 (86.6) | 130 (83.3) | 322 (88.0) | |
Yes | 70 (13.4) | 26 (16.7) | 44 (12.0) | |
MUC-AC, n (%) | 0.064 | |||
No | 494 (94.6) | 152 (97.4) | 342 (93.4) | |
Yes | 28 (5.4) | 4 (2.6) | 24 (6.6) | |
P63, n (%) | 0.184 | |||
No | 483 (92.5) | 148 (94.9) | 335 (91.5) | |
Yes | 39 (7.5) | 8 (5.1) | 31 (8.5) | |
CyclinD1, n (%) | 0.07 | |||
No | 493 (94.4) | 143 (91.7) | 350 (95.6) | |
Yes | 29 (5.6) | 13 (8.3) | 16 (4.4) | |
EMA, n (%) | 0.156 | |||
No | 496 (95.0) | 145 (92.9) | 351 (95.9) | |
Yes | 26 (5.0) | 11 (7.1) | 15 (4.1) | |
CD31, n (%) | 0.268 | |||
No | 491 (94.1) | 144 (92.3) | 347 (94.8) | |
Yes | 31 (5.9) | 12 (7.7) | 19 (5.2) | |
D2-40, n (%) | 0.403 | |||
No | 492 (94.3) | 145 (92.9) | 347 (94.8) | |
Yes | 30 (5.7) | 11 (7.1) | 19 (5.2) | |
Stretch fiber, n (%) | 0.893 | |||
No | 376 (72.0) | 113 (72.4) | 263 (71.9) | |
Yes | 146 (28.0) | 43 (27.6) | 103 (28.1) | |
PAS, n (%) | 0.82 | |||
No | 466 (89.3) | 140 (89.7) | 326 (89.1) | |
Yes | 56 (10.7) | 16 (10.3) | 40 (10.9) | |
PAS-D, n (%) | 0.828 | |||
No | 474 (90.8) | 141 (90.4) | 333 (91.0) | |
Yes | 48 (9.2) | 15 (9.6) | 33 (9.0) | |
Albumin (g/L), median (IQR) | 60.00 (57.92, 62.20) | 59.45 (57.68, 61.73) | 60.20 (58.02, 62.30) | 0.051 |
Lymphocyte (× 109/L), median (IQR) | 1.77 (1.44, 2.19) | 1.78 (1.42, 2.21) | 1.77 (1.45, 2.19) | 0.843 |
PNI (%), median (IQR) | 69.15 (66.00, 71.85) | 68.80 (65.84, 71.20) | 69.32 (66.11, 72.04) | 0.138 |
Neutrophil (× 109/L), median (IQR) | 3.00 (2.46, 3.89) | 3.06 (2.49, 3.87) | 2.96 (2.45, 3.89) | 0.813 |
Eosinophil (× 109/L), median (IQR) | 0.11 (0.06, 0.19) | 0.11 (0.07, 0.18) | 0.11 (0.06, 0.19) | 0.839 |
Basophil (× 109/L), median (IQR) | 0.03 (0.02, 0.04) | 0.03 (0.02, 0.04) | 0.03 (0.02, 0.04) | 0.89 |
Monocyte (× 109/L), median (IQR) | 0.42 (0.34, 0.51) | 0.42 (0.33, 0.50) | 0.42 (0.34, 0.51) | 0.718 |
Erythrocyte (× 1012/L), median (IQR) | 4.50 (4.20, 4.83) | 4.49 (4.11, 4.86) | 4.50 (4.23, 4.82) | 0.383 |
Hemoglobin (g/L), median (IQR) | 138.00 (128.00, 148.00) | 137.00 (126.00, 146.00) | 138.50 (129.00, 149.00) | 0.133 |
Platelet (× 109/L), median (IQR) | 234.00 (198.25, 267.00) | 232.00 (194.25, 264.00) | 235.00 (199.00, 269.00) | 0.319 |
NLR (%), median (IQR) | 1.72 (1.29, 2.24) | 1.75 (1.30, 2.27) | 1.71 (1.29, 2.23) | 0.928 |
PLR (%), median (IQR) | 132.06 (103.89, 163.59) | 130.94 (97.47, 164.23) | 133.94 (105.04, 163.06) | 0.345 |
MLR (%), median (IQR) | 0.23 (0.19, 0.29) | 0.22 (0.18, 0.29) | 0.23 (0.19, 0.29) | 0.438 |
dNLR (%), median (IQR) | 1.28 (1.01, 1.59) | 1.28 (0.99, 1.62) | 1.28 (1.01, 1.58) | 0.675 |
NLPR (%), median (IQR) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.782 |
SIRI (%), median (IQR) | 0.69 (0.49, 1.01) | 0.69 (0.48, 1.01) | 0.70 (0.49, 1.00) | 0.788 |
AISI (%), median (IQR) | 163.50 (108.03, 240.75) | 150.35 (105.01, 250.14) | 165.50 (110.25, 237.16) | 0.477 |
SII (%), median (IQR) | 396.04 (296.66, 533.27) | 383.11 (276.55, 546.01) | 404.92 (300.25, 528.57) | 0.418 |
Blood sugar(mmol/L), median (IQR) | 5.20 (4.75, 5.82) | 5.15 (4.75, 5.73) | 5.21 (4.75, 5.86) | 0.645 |
Complement C1q(mg/L), median (IQR) | 173.10 (150.62, 191.62) | 173.40 (150.48, 193.00) | 173.05 (150.80, 191.28) | 0.999 |
LDH (U/L), median (IQR) | 193.50 (173.00, 217.75) | 195.44 (178.00, 219.00) | 192.00 (172.00, 216.75) | 0.237 |
SA (mg/dL), median (IQR) | 54.03 (49.82, 59.00) | 54.03 (49.48, 58.40) | 54.03 (50.00, 59.18) | 0.583 |
5'-NT (U/L), median (IQR) | 4.00 (3.00, 5.00) | 4.00 (3.00, 5.00) | 4.00 (3.00, 5.00) | 0.606 |
Pro-GRP (pg/mL), median (IQR) | 41.96 (34.69, 45.88) | 41.96 (33.72, 44.41) | 41.96 (34.82, 46.14) | 0.603 |
SCC (ng/mL), median (IQR) | 1.10 (0.78, 1.97) | 1.10 (0.73, 1.97) | 1.10 (0.78, 1.97) | 0.766 |
Cyfra21-1 (ng/mL), median (IQR) | 2.32 (1.79, 2.62) | 2.32 (1.87, 2.70) | 2.32 (1.78, 2.58) | 0.536 |
CEA (ng/mL), median (IQR) | 2.32 (1.74, 2.97) | 2.32 (1.89, 3.15) | 2.32 (1.68, 2.92) | 0.159 |
CA125 (U/mL), median (IQR) | 10.72 (7.62, 11.20) | 10.72 (7.76, 12.03) | 10.50 (7.54, 10.90) | 0.207 |
NSE (ng/mL), median (IQR) | 19.45 (15.72, 20.60) | 19.45 (16.30, 20.60) | 19.45 (15.60, 20.58) | 0.544 |
Age (years), median (IQR) | 61.00 (54.00, 67.00) | 61.00 (54.00, 67.00) | 61.00 (54.00, 66.75) | 0.566 |
BMI (kg/m2), median (IQR) | 25.14 (23.05, 27.18) | 25.17 (22.86, 27.19) | 25.10 (23.15, 27.17) | 0.591 |
FEV1% predicted (%), median (IQR) | 104.36 (93.22, 116.15) | 102.90 (88.81, 113.14) | 105.29 (94.06, 117.16) | 0.063 |
MVV% predicted (%), median (IQR) | 104.06 (88.28, 115.19) | 101.32 (85.89, 114.83) | 104.89 (90.43, 116.36) | 0.038 |
Maximum diameter (cm), median (IQR) | 1.50 (1.20, 1.80) | 1.50 (1.20, 1.70) | 1.50 (1.20, 1.80) | 0.264 |
CTR (%), median (IQR) | 0.50 (0.00, 0.88) | 0.56 (0.09, 0.87) | 0.46 (0.00, 0.89) | 0.194 |
Ki-67 positive rate (%), median (IQR) | 0.00 (0.00, 1.00) | 0.00 (0.00, 0.00) | 0.00 (0.00, 2.00) | 0.283 |
Characteristics | Training Cohort (n = 366) | Validation cohort (n = 156) | ||||
---|---|---|---|---|---|---|
LNM (-) (n = 327) | LNM ( +) (n = 39) | p | LNM (-) (n = 134) | LNM ( +) (n = 22) | p | |
Gender, n (%) | 0.23 | |||||
Female | 168 (51.4) | 24 (61.5) | 78 (58.2) | 14 (63.6) | ||
Male | 159 (48.6) | 15 (38.5) | 56 (41.8) | 8 (36.4) | ||
Hypertension, n (%) | 0.297 | 0.965 | ||||
No | 216 (66.1) | 29 (74.4) | 92 (68.7) | 15 (68.2) | ||
Yes | 111 (33.9) | 10 (25.6) | 42 (31.3) | 7 (31.8) | ||
Diabetes, n (%) | 0.379 | 0.303 | ||||
No | 286 (87.5) | 36 (92.3) | 115 (85.8) | 17 (77.3) | ||
Yes | 41 (12.5) | 3 (7.7) | 19 (14.2) | 5 (22.7) | ||
COPD, n (%) | 0.548 | 0.479 | ||||
No | 324 (99.1) | 39 (100.0) | 131 (97.8) | 22 (100.0) | ||
Yes | 3 (0.9) | 0 (0.0) | 3 (2.2) | 0 (0.0) | ||
Smoking history, n (%) | 0.82 | 0.736 | ||||
Non-smoker | 229 (70.0) | 28 (71.8) | 99 (73.9) | 17 (77.3) | ||
Smoker | 98 (30.0) | 11 (28.2) | 35 (26.1) | 5 (22.7) | ||
Blood type, n (%) | 0.791 | 0.407 | ||||
A | 94 (28.7) | 12 (30.8) | 39 (29.1) | 5 (22.7) | ||
B | 127 (38.8) | 12 (30.8) | 46 (34.3) | 6 (27.3) | ||
AB | 34 (10.4) | 5 (12.8) | 14 (10.4) | 5 (22.7) | ||
O | 72 (22.0) | 10 (25.6) | 35 (26.1) | 6 (27.3) | ||
ASA, n (%) | 0.331 | 0.475 | ||||
1 | 28 (8.6) | 2 (5.1) | 9 (6.7) | 2 (9.1) | ||
2 | 288 (88.1) | 34 (87.2) | 120 (89.6) | 18 (81.8) | ||
3 | 11 (3.4) | 3 (7.7) | 5 (3.7) | 2 (9.1) | ||
Location, n (%) | 0.72 | 0.769 | ||||
Centrality | 40 (12.2) | 4 (10.3) | 15 (11.2) | 2 (9.1) | ||
Peripherality | 287 (87.8) | 35 (89.7) | 119 (88.8) | 20 (90.9) | ||
Shape, n (%) | 0.519 | 0.907 | ||||
Regularity | 109 (33.3) | 11 (28.2) | 47 (35.1) | 8 (36.4) | ||
Irregularity | 218 (66.7) | 28 (71.8) | 87 (64.9) | 14 (63.6) | ||
Spiculation, n (%) | 0.121 | 0.069 | ||||
No | 107 (32.7) | 8 (20.5) | 44 (32.8) | 3 (13.6) | ||
Yes | 220 (67.3) | 31 (79.5) | 90 (67.2) | 19 (86.4) | ||
Cavitation sign, n (%) | 0.925 | 0.132 | ||||
No | 262 (80.1) | 31 (79.5) | 105 (78.4) | 14 (63.6) | ||
Yes | 65 (19.9) | 8 (20.5) | 29 (21.6) | 8 (36.4) | ||
Calcification, n (%) | 0.437 | NA | ||||
No | 322 (98.5) | 39 (100.0) | 134 (100.0) | 22 (100.0) | ||
Yes | 5 (1.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
Vascular penetration sign, n (%) | 0.37 | 0.974 | ||||
No | 89 (27.2) | 8 (20.5) | 37 (27.6) | 6 (27.3) | ||
Yes | 238 (72.8) | 31 (79.5) | 97 (72.4) | 16 (72.7) | ||
Pleural adhesions, n (%) | 0.01 | 0.022 | ||||
No | 128 (39.1) | 7 (17.9) | 52 (38.8) | 3 (13.6) | ||
Yes | 199 (60.9) | 32 (82.1) | 82 (61.2) | 19 (86.4) | ||
Bronchus sign, n (%) | 0.185 | 0.249 | ||||
No | 227 (69.4) | 23 (59.0) | 90 (67.2) | 12 (54.5) | ||
Yes | 100 (30.6) | 16 (41.0) | 44 (32.8) | 10 (45.5) | ||
Lobulation, n (%) | 0.02 | 0.065 | ||||
No | 165 (50.5) | 12 (30.8) | 77 (57.5) | 8 (36.4) | ||
Yes | 162 (49.5) | 27 (69.2) | 57 (42.5) | 14 (63.6) | ||
Lymph node enlargement sign, n (%) | 0.251 | 0.907 | ||||
No | 268 (82.0) | 29 (74.4) | 111 (82.8) | 18 (81.8) | ||
Yes | 59 (18.0) | 10 (25.6) | 23 (17.2) | 4 (18.2) | ||
Pleural effusion sign, n (%) | 0.487 | 0.564 | ||||
No | 323 (98.8) | 39 (100.0) | 132 (98.5) | 22 (100.0) | ||
Yes | 4 (1.2) | 0 (0.0) | 2 (1.5) | 0 (0.0) | ||
Lepidic, n (%) | 0.049 | 0.153 | ||||
No | 100 (30.6) | 18 (46.2) | 35 (26.1) | 9 (40.9) | ||
Yes | 227 (69.4) | 21 (53.8) | 99 (73.9) | 13 (59.1) | ||
Acinar, n (%) | 0.638 | 0.42 | ||||
No | 65 (19.9) | 9 (23.1) | 21 (15.7) | 2 (9.1) | ||
Yes | 262 (80.1) | 30 (76.9) | 113 (84.3) | 20 (90.9) | ||
Papillary, n (%) | 0.319 | 0.029 | ||||
No | 203 (62.1) | 21 (53.8) | 82 (61.2) | 8 (36.4) | ||
Yes | 124 (37.9) | 18 (46.2) | 52 (38.8) | 14 (63.6) | ||
Micropapillary, n (%) | 0.003 | < 0.001 | ||||
No | 273 (83.5) | 25 (64.1) | 112 (83.6) | 11 (50.0) | ||
Yes | 54 (16.5) | 14 (35.9) | 22 (16.4) | 11 (50.0) | ||
Solid, n (%) | < 0.001 | 0.015 | ||||
No | 313 (95.7) | 31 (79.5) | 128 (95.5) | 18 (81.8) | ||
Yes | 14 (4.3) | 8 (20.5) | 6 (4.5) | 4 (18.2) | ||
Mucinous, n (%) | 0.015 | 0.979 | ||||
No | 283 (86.5) | 28 (71.8) | 116 (86.6) | 19 (86.4) | ||
Yes | 44 (13.5) | 11 (28.2) | 18 (13.4) | 3 (13.6) | ||
CK5/6, n (%) | < 0.001 | < 0.001 | ||||
No | 318 (97.2) | 26 (66.7) | 133 (99.3) | 19 (86.4) | ||
Yes | 9 (2.8) | 13 (33.3) | 1 (0.7) | 3 (13.6) | ||
CK7, n (%) | 0.033 | 0.003 | ||||
No | 252 (77.1) | 24 (61.5) | 106 (79.1) | 11 (50.0) | ||
Yes | 75 (22.9) | 15 (38.5) | 28 (20.9) | 11 (50.0) | ||
TTF-1, n (%) | 0.001 | < 0.001 | ||||
No | 241 (73.7) | 19 (48.7) | 104 (77.6) | 9 (40.9) | ||
Yes | 86 (26.3) | 20 (51.3) | 30 (22.4) | 13 (59.1) | ||
Napsin A, n (%) | < 0.001 | < 0.001 | ||||
No | 299 (91.4) | 23 (59.0) | 119 (88.8) | 11 (50.0) | ||
Yes | 28 (8.6) | 16 (41.0) | 15 (11.2) | 11 (50.0) | ||
MUC-AC, n (%) | 0.286 | 0.526 | ||||
No | 304 (93.0) | 38 (97.4) | 131 (97.8) | 21 (95.5) | ||
Yes | 23 (7.0) | 1 (2.6) | 3 (2.2) | 1 (4.5) | ||
P63, n (%) | < 0.001 | < 0.001 | ||||
No | 310 (94.8) | 25 (64.1) | 131 (97.8) | 17 (77.3) | ||
Yes | 17 (5.2) | 14 (35.9) | 3 (2.2) | 5 (22.7) | ||
CyclinD1, n (%) | 0.057 | < 0.001 | ||||
No | 315 (96.3) | 35 (89.7) | 129 (96.3) | 14 (63.6) | ||
Yes | 12 (3.7) | 4 (10.3) | 5 (3.7) | 8 (36.4) | ||
EMA, n (%) | < 0.001 | < 0.001 | ||||
No | 319 (97.6) | 32 (82.1) | 130 (97.0) | 15 (68.2) | ||
Yes | 8 (2.4) | 7 (17.9) | 4 (3.0) | 7 (31.8) | ||
CD31, n (%) | 0.023 | < 0.001 | ||||
No | 313 (95.7) | 34 (87.2) | 129 (96.3) | 15 (68.2) | ||
Yes | 14 (4.3) | 5 (12.8) | 5 (3.7) | 7 (31.8) | ||
D2-40, n (%) | < 0.001 | < 0.001 | ||||
No | 315 (96.3) | 32 (82.1) | 129 (96.3) | 16 (72.7) | ||
Yes | 12 (3.7) | 7 (17.9) | 5 (3.7) | 6 (27.3) | ||
Stretch fiber, n (%) | 0.008 | 0.043 | ||||
No | 242 (74.0) | 21 (53.8) | 101 (75.4) | 12 (54.5) | ||
Yes | 85 (26.0) | 18 (46.2) | 33 (24.6) | 10 (45.5) | ||
PAS, n (%) | < 0.001 | 0.005 | ||||
No | 305 (93.3) | 21 (53.8) | 124 (92.5) | 16 (72.7) | ||
Yes | 22 (6.7) | 18 (46.2) | 10 (7.5) | 6 (27.3) | ||
PAS-D, n (%) | 0.001 | < 0.001 | ||||
No | 303 (92.7) | 30 (76.9) | 127 (94.8) | 14 (63.6) | ||
Yes | 24 (7.3) | 9 (23.1) | 7 (5.2) | 8 (36.4) | ||
Albumin (g/L), median (IQR) | 60.40 (58.30, 62.50) | 58.80 (56.30, 60.40) | 0.004 | 59.60 (57.70, 61.90) | 58.55 (57.62, 60.13) | 0.191 |
Lymphocyte (× 109/L), median (IQR) | 1.81 (1.46, 2.21) | 1.59 (1.28, 1.85) | 0.015 | 1.83 (1.42, 2.27) | 1.63 (1.43, 2.01) | 0.326 |
PNI (%), median (IQR) | 69.65 (66.45, 72.25) | 66.00 (64.55, 69.22) | < 0.001 | 69.05 (66.01, 71.39) | 67.28 (64.33, 69.30) | 0.072 |
Neutrophil (× 109/L), median (IQR) | 2.94 (2.45, 3.90) | 3.02 (2.64, 3.39) | 0.934 | 3.07 (2.44, 3.85) | 3.05 (2.81, 3.95) | 0.341 |
Eosinophil (× 109/L), median (IQR) | 0.11 (0.06, 0.18) | 0.11 (0.07, 0.21) | 0.689 | 0.11 (0.07, 0.21) | 0.10 (0.07, 0.15) | 0.402 |
Basophil (× 109/L), median (IQR) | 0.03 (0.02, 0.04) | 0.03 (0.02, 0.04) | 0.716 | 0.03 (0.02, 0.04) | 0.03 (0.03, 0.04) | 0.524 |
Monocyte (× 109/L), median (IQR) | 0.42 (0.34, 0.51) | 0.40 (0.33, 0.52) | 0.994 | 0.42 (0.33, 0.50) | 0.42 (0.36, 0.50) | 0.704 |
Erythrocyte (× 1012/L), median (IQR) | 4.51 (4.24, 4.82) | 4.50 (4.20, 4.82) | 0.898 | 4.48 (4.09, 4.85) | 4.58 (4.34, 4.86) | 0.367 |
Hemoglobin (g/L), median (IQR) | 138.00 (129.00, 149.00) | 139.00 (125.00, 148.00) | 0.409 | 136.50 (126.00, 145.75) | 137.50 (126.50, 145.00) | 0.923 |
Platelet (× 109/L), median (IQR) | 232.00 (198.50, 264.50) | 261.00 (231.50, 288.50) | 0.013 | 230.00 (191.00, 264.00) | 242.50 (211.25, 286.00) | 0.179 |
NLR (%), median (IQR) | 1.70 (1.26, 2.23) | 1.91 (1.57, 2.24) | 0.042 | 1.66 (1.27, 2.12) | 2.03 (1.70, 2.43) | 0.026 |
PLR (%), median (IQR) | 130.66 (104.47, 159.12) | 161.74 (136.77, 181.94) | < 0.001 | 127.15 (93.63, 157.73) | 155.21 (116.53, 180.74) | 0.043 |
MLR (%), median (IQR) | 0.23 (0.18, 0.29) | 0.27 (0.22, 0.32) | 0.012 | 0.22 (0.18, 0.28) | 0.25 (0.20, 0.33) | 0.182 |
dNLR (%), median (IQR) | 1.28 (1.01, 1.58) | 1.40 (1.12, 1.60) | 0.147 | 1.24 (0.97, 1.57) | 1.51 (1.28, 1.69) | 0.012 |
NLPR (%), median (IQR) | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.496 | 0.01 (0.01, 0.01) | 0.01 (0.01, 0.01) | 0.212 |
SIRI (%), median (IQR) | 0.69 (0.47, 1.02) | 0.80 (0.63, 0.92) | 0.068 | 0.65 (0.47, 0.98) | 0.79 (0.57, 1.33) | 0.108 |
AISI (%), median (IQR) | 163.03 (105.84, 232.89) | 221.50 (144.41, 264.92) | 0.017 | 147.89 (100.00, 242.84) | 181.92 (135.84, 375.84) | 0.056 |
SII (%), median (IQR) | 389.76 (298.64, 511.21) | 519.12 (343.84, 622.08) | 0.006 | 369.06 (273.13, 515.99) | 504.51 (390.20, 594.27) | 0.013 |
Blood sugar(mmol/L), median (IQR) | 5.22 (4.78, 5.86) | 5.10 (4.62, 5.76) | 0.172 | 5.11 (4.73, 5.67) | 5.48 (4.96, 6.27) | 0.117 |
Complement C1q(mg/L), median (IQR) | 171.00 (149.90, 188.55) | 189.20 (163.10, 206.95) | 0.002 | 170.80 (149.72, 192.62) | 179.80 (168.00, 192.75) | 0.089 |
LDH (U/L), median (IQR) | 191.00 (172.00, 215.50) | 195.89 (173.00, 229.50) | 0.209 | 193.00 (176.50, 219.75) | 196.50 (184.75, 207.00) | 0.996 |
SA (mg/dL), median (IQR) | 54.00 (49.75, 58.80) | 57.10 (51.30, 63.95) | 0.033 | 54.03 (49.12, 58.58) | 56.00 (52.37, 58.25) | 0.151 |
5'-NT (U/L), median (IQR) | 4.00 (3.00, 5.00) | 4.00 (3.00, 4.62) | 0.497 | 4.00 (3.00, 5.00) | 4.00 (4.00, 5.00) | 0.149 |
Pro-GRP (pg/mL), median (IQR) | 41.96 (34.69, 45.59) | 41.96 (35.90, 49.95) | 0.335 | 41.96 (32.44, 44.34) | 41.96 (41.34, 45.13) | 0.069 |
SCC (ng/mL), median (IQR) | 1.10 (0.78, 1.97) | 1.10 (0.94, 1.96) | 0.706 | 1.06 (0.72, 1.97) | 1.36 (0.76, 1.97) | 0.273 |
Cyfra21-1 (ng/mL), median (IQR) | 2.32 (1.80, 2.58) | 2.32 (1.73, 2.57) | 0.697 | 2.32 (1.88, 2.70) | 2.32 (1.72, 2.32) | 0.674 |
CEA (ng/mL), median (IQR) | 2.32 (1.75, 2.92) | 2.32 (1.09, 2.78) | 0.251 | 2.32 (1.80, 2.97) | 2.32 (2.32, 3.83) | 0.109 |
CA125 (U/mL), median (IQR) | 10.30 (7.40, 10.72) | 10.72 (9.84, 12.80) | 0.002 | 10.71 (7.61, 11.28) | 11.41 (10.72, 14.02) | 0.002 |
NSE (ng/mL), median (IQR) | 19.45 (15.50, 20.05) | 19.45 (16.95, 22.95) | 0.239 | 19.45 (15.93, 20.60) | 19.45 (18.27, 20.16) | 0.488 |
Age (years), median (IQR) | 62.00 (54.00, 67.00) | 56.00 (48.50, 64.00) | 0.017 | 62.00 (54.25, 68.00) | 56.00 (50.75, 63.50) | 0.034 |
BMI (kg/m2), median (IQR) | 24.97 (23.04, 27.04) | 26.37 (24.53, 29.94) | 0.005 | 24.91 (22.59, 27.02) | 25.41 (24.25, 28.07) | 0.069 |
FEV1% predicted (%), median (IQR) | 105.30 (94.90, 117.40) | 97.01 (85.34, 109.50) | 0.037 | 102.69 (88.96, 114.94) | 104.15 (85.17, 110.00) | 0.563 |
MVV% predicted (%), median (IQR) | 105.23 (90.91, 117.04) | 99.47 (87.00, 111.57) | 0.126 | 101.32 (85.28, 114.90) | 99.50 (86.96, 114.40) | 0.776 |
Maximum diameter (cm), median (IQR) | 1.50 (1.20, 1.75) | 1.60 (1.50, 1.90) | 0.001 | 1.45 (1.10, 1.60) | 1.60 (1.40, 1.95) | 0.013 |
CTR (%), median (IQR) | 0.43 (0.00, 0.85) | 0.85 (0.40, 1.00) | < 0.001 | 0.50 (0.00, 0.73) | 0.79 (0.60, 1.00) | 0.004 |
Ki-67 positive rate (%), median (IQR) | 0.00 (0.00, 1.25) | 0.00 (0.00, 15.00) | 0.103 | 0.00 (0.00, 0.00) | 0.00 (0.00, 14.38) | 0.002 |
Identifying risk factors for lymph node metastasis
Characteristics | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|
OR (95%CI) | P | OR (95%CI) | P | |
Age | 0.959 (0.927, 0.991) | 0.013 | 0.934 (0.871, 0.996) | < 0.001 |
SA | 1.041 (1.003, 1.081) | 0.033 | 1.025 (0.937, 1.109) | 0.008 |
CA125 | 1.045 (1.006, 1.094) | 0.028 | 1.103 (1.021, 1.189) | 0.042 |
Mucinous | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.527 (1.135, 5.324) | 0.018 | 1.729 (0.371, 7.519) | 0.003 |
Napsin A | ||||
No | Ref | Ref | Ref | Ref |
Yes | 7.429 (3.494, 15.681) | < 0.001 | 2.704 (0.489, 15.541) | 0.007 |
CK5/6 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 17.667 (6.993, 46.668) | < 0.001 | 18.668 (2.938, 154.991) | 0.042 |
PAS-D | ||||
No | Ref | Ref | Ref | Ref |
Yes | 3.788 (1.548, 8.676) | 0.002 | 3.521 (0.605, 19.102) | 0.067 |
CK7 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.100 (1.030, 4.171) | 0.036 | 0.146 (0.021, 0.935) | 0.123 |
PAS | ||||
No | Ref | Ref | Ref | Ref |
Yes | 11.883 (5.542, 25.739) | < 0.001 | 1.673 (0.307, 7.799) | 0.148 |
Pleural adhesions | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.940 (1.332, 7.436) | 0.013 | 3.516 (0.800, 19.883) | 0.21 |
D2-40 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 5.742 (2.015, 15.355) | 0.001 | 4.325 (0.285, 89.145) | 0.252 |
TTF-1 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.950 (1.500, 5.827) | 0.002 | 3.817 (0.668, 21.137) | 0.253 |
CD31 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 3.288 (1.013, 9.196) | 0.031 | 0.393 (0.013, 10.772) | 0.3 |
Solid | ||||
No | Ref | Ref | Ref | Ref |
Yes | 5.770 (2.159, 14.602) | < 0.001 | 1.925 (0.246, 13.577) | 0.47 |
Micropapillary | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.831 (1.355, 5.735) | 0.004 | 2.189 (0.495, 9.065) | 0.515 |
Stretch fiber | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.440 (1.231, 4.801) | 0.01 | 2.134 (0.578, 7.992) | 0.528 |
EMA, n (%) | ||||
No | Ref | Ref | Ref | Ref |
Yes | 8.723 (2.889, 25.881) | < 0.001 | 2.237 (0.213, 22.148) | 0.588 |
P63 | ||||
No | Ref | Ref | Ref | Ref |
Yes | 10.212 (4.487, 23.219) | < 0.001 | 9.324 (1.994, 52.880) | 0.608 |
Lobulation | ||||
No | Ref | Ref | Ref | Ref |
Yes | 2.292 (1.146, 4.838) | 0.023 | 2.316 (0.647, 9.247) | 0.989 |
Maximum Diameter | 5.159 (1.965, 14.589) | 0.001 | 3.651 (0.759, 20.700) | 0.119 |
FEV1% predicted | 0.982 (0.964, 1.000) | 0.045 | 0.979 (0.946, 1.013) | 0.12 |
PLR | 1.010 (1.004, 1.016) | 0.001 | 0.994 (0.954, 1.029) | 0.067 |
Lymphocyte | 0.475 (0.235, 0.896) | 0.03 | 0.087 (0.001, 2.061) | 0.199 |
BMI | 1.172 (1.067, 1.288) | 0.001 | 1.367 (1.161, 1.642) | 0.21 |
CTR | 5.724 (2.351, 15.258) | < 0.001 | 0.988 (0.171, 5.685) | 0.284 |
PNI | 0.925 (0.876, 0.977) | 0.005 | NA (NA, NA) | 0.352 |
Ki-67 positive rate | 1.029 (1.010, 1.046) | 0.001 | 0.990 (0.949, 1.028) | 0.495 |
Complement C1q | 1.018 (1.007, 1.029) | 0.001 | 1.020 (0.999, 1.042) | 0.553 |
Platelet | 1.006 (1.001, 1.011) | 0.016 | 1.012 (0.989, 1.041) | 0.747 |
Albumin | 0.942 (0.888, 1.003) | 0.047 | 1.010 (0.896, 1.176) | 0.886 |
Acinar | ||||
No | Ref | Ref | ||
Yes | 0.827 (0.388, 1.926) | 0.639 | ||
ASA | ||||
1 | Ref | Ref | ||
2 | 1.653 (0.467, 10.515) | 0.505 | ||
3 | 3.818 (0.561, 32.139) | 0.171 | ||
Blood type | ||||
A | Ref | Ref | ||
B | 0.740 (0.315, 1.736) | 0.484 | ||
AB | 1.152 (0.346, 3.360) | 0.804 | ||
O | 1.088 (0.436, 2.662) | 0.853 | ||
Bronchus sign | ||||
No | Ref | Ref | ||
Yes | 1.579 (0.788, 3.099) | 0.188 | ||
Calcification | ||||
No | Ref | Ref | ||
Yes | 0.000 (NA, NA) | 0.989 | ||
Cavitation sign | ||||
No | Ref | Ref | ||
Yes | 1.040 (0.429, 2.270) | 0.925 | ||
COPD | ||||
No | Ref | Ref | ||
Yes | 0.000 (NA, NA) | 0.987 | ||
CyclinD1 | ||||
No | Ref | Ref | ||
Yes | 3.000 (0.805, 9.151) | 0.069 | ||
Diabetes | ||||
No | Ref | Ref | ||
Yes | 0.581 (0.136, 1.708) | 0.384 | ||
Gender | ||||
Female | Ref | Ref | ||
Male | 0.660 (0.328, 1.292) | 0.232 | ||
Hypertension | ||||
No | Ref | Ref | ||
Yes | 0.671 (0.301, 1.384) | 0.3 | ||
Lepidic | ||||
No | Ref | Ref | ||
Yes | 0.514 (0.262, 1.015) | 0.052 | ||
Location | ||||
Centrality | Ref | Ref | ||
Peripherality | 1.220 (0.456, 4.238) | 0.72 | ||
Lymph node enlargement sign | ||||
No | Ref | Ref | ||
Yes | 1.566 (0.693, 3.295) | 0.255 | ||
MUC-AC | ||||
No | Ref | Ref | ||
Yes | 0.348 (0.019, 1.726) | 0.308 | ||
Papillary | ||||
No | Ref | Ref | ||
Yes | 1.403 (0.713, 2.737) | 0.32 | ||
Pleural effusion sign | ||||
No | Ref | Ref | ||
Yes | 0.000 (NA, NA) | 0.985 | ||
Shape | ||||
Regularity | Ref | Ref | ||
Irregularity | 1.273 (0.626, 2.758) | 0.52 | ||
Smoking history | ||||
Non-smoker | Ref | Ref | ||
Smoker | 0.918 (0.423, 1.870) | 0.82 | ||
Spiculation | ||||
No | Ref | Ref | ||
Yes | 1.885 (0.876, 4.528) | 0.126 | ||
Vascular penetration sign | ||||
No | Ref | Ref | ||
Yes | 1.449 (0.671, 3.492) | 0.372 | ||
Cyfra21-1 | 0.934 (0.623, 1.078) | 0.684 | ||
AISI | 1.000 (0.999, 1.001) | 0.495 | ||
Basophil | 0.501 (0.000, 48.590) | 0.856 | ||
Blood Sugar | 0.802 (0.556, 1.072) | 0.187 | ||
CEA | 0.939 (0.717, 1.151) | 0.602 | ||
dNLR | 1.062 (0.636, 1.543) | 0.778 | ||
Eosinophil | 1.375 (0.221, 4.520) | 0.618 | ||
Erythrocyte | 0.920 (0.431, 1.956) | 0.829 | ||
Hemoglobin | 0.981 (0.959, 1.002) | 0.078 | ||
LDH | 1.006 (0.998, 1.015) | 0.122 | ||
MLR | 1.803 (0.830, 3.913) | 0.096 | ||
Monocyte | 1.168 (0.731, 1.673) | 0.366 | ||
MVV% predicted | 0.987 (0.971, 1.001) | 0.097 | ||
Neutrophil | 0.945 (0.704, 1.185) | 0.668 | ||
NLPR | 0.000 (NA, NA) | 0.597 | ||
NLR | 1.023 (0.775, 1.215) | 0.825 | ||
NSE | 1.029 (0.988, 1.067) | 0.133 | ||
Pro_GRP | 1.005 (0.979, 1.028) | 0.695 | ||
SCC | 0.960 (0.562, 1.451) | 0.867 | ||
SII | 1.000 (1.000, 1.001) | 0.265 | ||
SIRI | 1.023 (0.799, 1.170) | 0.781 | ||
5'-NT | 0.995 (0.747, 1.271) | 0.973 |
Frequency of targeted gene alterations
Nomogram construction
Predictive performance and validation of the nomogram
Characteristics | Value |
---|---|
Threshold | 0.089 |
Specificity | 0.786 |
Sensitivity | 0.795 |
Accuracy | 0.787 |
TN | 257 |
TP | 31 |
FN | 8 |
FP | 70 |
NPV | 0.97 |
PPV | 0.307 |
FDR | 0.693 |
FPR | 0.214 |
TPR | 0.795 |
TNR | 0.786 |
FNR | 0.205 |
1-specificity | 0.214 |
1-sensitivity | 0.205 |
1-accuracy | 0.213 |
1-npv | 0.03 |
1-ppv | 0.693 |
Precision | 0.307 |
Recall | 0.795 |
Youden | 1.581 |
Closest.topleft | 0.088 |