Significance statement
Introduction
Methods
Patient selection
Characteristics | Overall N(%) |
---|---|
Sample size | 488 |
Sex | |
Male | 128 (26.2) |
Female | 360 (73.8) |
Age (years) | |
< 45 | 240 (49.2) |
≥ 45 | 248 (50.8) |
Combined benign thyroid disease | |
No | 262 (53.7) |
Nodular goiter | 138 (28.3) |
Lymphocytic thyroiditis | 67 (13.7) |
Both | 21 (4.3) |
Surgical method | |
Unilateral | 213 (43.6) |
Total | 275 (56.4) |
BRAF V600E gene mutation | |
No | 99 (20.3) |
Yes | 389 (79.7) |
Lymph node metastasis | |
No | 251 (51.4) |
Central | 173 (35.5) |
Lateral | 11 (2.2) |
Both | 53 (10.9) |
Maximum diameter of thyroid nodules | |
< 10 mm | 210 (43.0) |
10–20 mm | 204 (41.8) |
> 20 mm | 74 (15.2) |
Nodule location | |
Upper 1/3 | 102 (20.9) |
Middle 1/3 | 146 (29.9) |
Lower 1/3 | 77 (15.8) |
Isthmus | 63 (12.9) |
Whole | 100 (20.5) |
Aspect Ratio | |
< 1 | 284 (58.2) |
≥ 1 | 204 (41.8) |
Microcalcification | |
No | 127 (26.0) |
Yes | 361 (74.0) |
Nodule boundary | |
Clear | 199 (40.8) |
Blurred | 289 (59.2) |
Capsular invasion | |
No | 275 (56.4) |
Close | 65 (13.3) |
Invasion | 148 (30.3) |
Number of lesions | |
Unifocal | 346 (70.9) |
Multifocal | 142 (29.1) |
ACR-TIRADS classification | |
3 | 20 (4.1) |
4a | 274 (56.1) |
4b | 153 (31.4) |
4c | 27 (5.5) |
5 | 12 (2.5) |
6 | 2 (0.4) |
Clinicopathological features
Detection of BRAF V600E gene mutation status by second-generation sequencing
Construction and validation of the nomogram prediction model
1D-CNN model building and training
Subgroup analysis and validation
Characteristics | Overall N(%) | Subclinical metastasis group | Clinical metastasis group | ||
---|---|---|---|---|---|
Nonmetastasis N(%) | Metastasis N(%) | Nonmetastasis N(%) | Metastasis N(%) | ||
Sample size | 477 | 238 | 166 | 13 | 60 |
Sex | |||||
Male | 124 (26.0) | 53 (22.27) | 47 (28.31) | 3 (23.08) | 21 (35.00) |
Female | 353 (74.0) | 185 (77.73) | 119 (71.69) | 10 (76.92) | 39 (65.00) |
Age (years) | |||||
< 45 | 234 (49.1) | 85 (35.71) | 99 (59.64) | 3 (23.08) | 47 (78.33) |
≥ 45 | 243(50.9) | 153 (64.29) | 67 (40.36) | 10 (76.92) | 13 (21.67) |
Combined benign thyroid disease | |||||
No | 257 (53.9) | 121 (50.84) | 96 (57.83) | 7 (53.85) | 33 (55.00) |
Nodular goiter | 133 (27.9) | 70 (29.41) | 42 (25.30) | 3 (23.08) | 18 (30.00) |
Lymphocytic thyroiditis | 66 (13.8) | 32 (13.45) | 24 (14.46) | 2 (15.38) | 8 (13.33) |
Both | 21 (4.4) | 15 (6.30) | 4 (2.41) | 1 (7.69) | 1 (1.67) |
Surgical method | |||||
Unilateral | 230 (48.2) | 119 (50.00) | 77 (46.39) | 4 (30.77) | 30 (50.00) |
Total | 247 (51.8) | 119 (50.00) | 89 (53.61) | 9 (69.23) | 30 (50.00) |
BRAF V600E gene mutation | |||||
No | 97 (20.3) | 76 (31.93) | 14 (8.43) | 4 (30.77) | 3 (5.00) |
Yes | 380 (79.7) | 162 (68.07) | 152 (91.57) | 9 (69.23) | 57 (95.00) |
Maximum diameter of thyroid nodules | |||||
< 10 mm | 207 (43.4) | 132 (55.46) | 61 (36.75) | 5 (38.46) | 9 (15.00) |
10–20 mm | 201 (42.1) | 86 (36.13) | 79 (47.59) | 8 (61.54) | 28 (46.67) |
> 20 mm | 69 (14.5) | 20 (8.40) | 26 (15.66) | 0 (0.00) | 23 (38.33) |
Nodule location | |||||
Upper 1/3 | 98 (20.6) | 49 (20.59) | 30 (18.07) | 4 (30.77) | 15 (25.00) |
Middle 1/3 | 145 (30.4) | 75 (31.51) | 51 (30.72) | 4 (30.77) | 15 (25.00) |
Lower 1/3 | 76 (15.9) | 34 (14.29) | 32 (19.28) | 2 (15.38) | 8 (13.33) |
Isthmus | 62 (13.0) | 33 (13.87) | 23 (13.86) | 2 (15.38) | 4 (6.67) |
Whole | 96 (20.1) | 47 (19.75) | 30 (18.07) | 1 (7.69) | 18 (30.00) |
Aspect Ratio | |||||
< 1 | 274 (57.4) | 132 (55.46) | 98 (59.04) | 7 (53.85) | 37 (61.67) |
≥ 1 | 203 (42.6) | 106 (44.54) | 68 (40.96) | 6 (46.15) | 23 (38.33) |
Microcalcification | |||||
No | 123 (25.8) | 70 (29.41) | 40 (24.10) | 2 (15.38) | 11 (18.33) |
Yes | 354 (74.2) | 168 (70.59) | 126 (75.90) | 11 (84.62) | 49 (81.67) |
Nodule boundary | |||||
Clear | 192 (40.3) | 103 (43.28) | 63 (37.95) | 5 (38.46) | 21 (35.00) |
Blurred | 285 (59.7) | 135 (56.72) | 103 (62.05) | 8 (61.54) | 39 (65.00) |
Capsular invasion | |||||
No | 268 (56.2) | 143 (60.08) | 92 (55.42) | 10 (76.92) | 23 (38.33) |
Close | 63 (13.2) | 39 (16.39) | 20 (12.05) | 0 (0.00) | 4 (6.67) |
Invasion | 146 (30.6) | 56 (23.53) | 54 (32.53) | 3 (23.08) | 33 (55.00) |
Number of lesions | |||||
Unifocal | 339 (71.1) | 177 (74.37) | 116 (69.88) | 9 (69.23) | 37 (61.67) |
Multifocal | 138 (28.9) | 61 (25.63) | 50 (30.12) | 4 (30.77) | 23 (38.33) |
ACR-TIRADS classification | |||||
3 | 19 (4.00) | 7 (2.94) | 9 (5.42) | 0 (0.00) | 3 (5.00) |
4a | 268 (56.2) | 136 (57.14) | 92 (55.42) | 11 (84.62) | 29 (48.33) |
4b | 149 (31.2) | 70 (29.41) | 55 (33.13) | 2 (15.38) | 22 (36.67) |
4c | 27 (5.66) | 18 (7.56) | 5 (3.01) | 0 (0.00) | 4 (6.67) |
5 | 12 (2.52) | 6 (2.52) | 5 (3.01) | 0 (0.00) | 1 (1.67) |
6 | 2 (0.42) | 1 (0.42) | 0 (0.00) | 0 (0.00) | 1 (1.67) |
Statistical analysis
Results
CLNM is associated with several clinicopathological features
Characteristics | Overall N(%) | Nonmetastasis N(%) | Metastasis N(%) | X2 | P -value |
---|---|---|---|---|---|
Sample size | 477 | 251 | 226 | ||
Sex | |||||
Male | 124 (26.0) | 56 (22.3) | 68 (30.0) | 3.739 | 0.053 |
Female | 353 (74.0) | 195 (77.7) | 158 (70.0) | ||
Age (years) | |||||
< 45 | 234 (49.1) | 88 (35.1) | 146 (64.6) | 41.530 | < 0.001 |
≥ 45 | 243(50.9) | 163 (64.9) | 80 (35.4) | ||
Combined benign thyroid disease | |||||
No | 257 (53.9) | 128 (51.0) | 129 (57.1) | 5.803 | 0.122 |
Nodular goiter | 133 (27.9) | 73 (29.1) | 60 (26.5) | ||
Lymphocytic thyroiditis | 66 (13.8) | 34 (13.5) | 32 (14.2) | ||
Both | 21 (4.4) | 16 (6.4) | 5 (2.2) | ||
Surgical method | |||||
Unilateral | 230 (48.2) | 123 (49.0) | 107 (47.3) | 0.073 | 0.787 |
Total | 247 (51.8) | 128 (51.0) | 119 (52.7) | ||
BRAF V600E gene mutation | |||||
No | 97 (20.3) | 80 (31.9) | 17 (7.5) | 43.527 | < 0.001 |
Yes | 380 (79.7) | 171 (68.1) | 209 (92.5) | ||
Maximum diameter of thyroid nodules | |||||
< 10 mm | 207 (43.4) | 137 (54.6) | 70 (31.0) | 33.497 | < 0.001 |
10–20 mm | 201 (42.1) | 94 (37.4) | 107 (47.3) | ||
> 20 mm | 69 (14.5) | 20(8.0) | 49 (21.7) | ||
Nodule location | |||||
Upper 1/3 | 98 (20.6) | 53 (21.1) | 45 (19.9) | 1.756 | 0.781 |
Middle 1/3 | 145 (30.4) | 79 (31.5) | 66 (29.2) | ||
Lower 1/3 | 76 (15.9) | 36 (14.3) | 40 (17.7) | ||
Isthmus | 62 (13.0) | 35 (14.0) | 27 (12.0) | ||
Whole | 96 (20.1) | 48 (19.1) | 48 (21.2) | ||
Aspect Ratio | |||||
< 1 | 274 (57.4) | 139 (55.4) | 135 (59.7) | 0.923 | 0.337 |
≥ 1 | 203 (42.6) | 112 (44.6) | 91 (40.3) | ||
Microcalcification | |||||
No | 123 (25.8) | 72 (28.7) | 51 (22.6) | 2.327 | 0.127 |
Yes | 354 (74.2) | 179 (71.3) | 175 (77.4) | ||
Nodule boundary | |||||
Clear | 192 (40.3) | 108 (43.0) | 84 (37.2) | 1.698 | 0.193 |
Blurred | 285 (59.7) | 143 (57.0) | 142 (62.8) | ||
Capsular invasion | |||||
No | 268 (56.2) | 153 (61.0) | 115 (50.9) | 13.055 | 0.001 |
Close | 63 (13.2) | 39 (15.5) | 24 (10.6) | ||
Invasion | 146 (30.6) | 59 (23.5) | 87 (38.5) | ||
Number of lesions | |||||
Unifocal | 339 (71.1) | 186 (74.1) | 153 (67.7) | 2.372 | 0.123 |
Multifocal | 138 (28.9) | 65 (25.9) | 73 (32.3) | ||
ACR-TIRADS classification | |||||
3 | 19 (4.00) | 7 (2.79) | 12 (5.31) | 5.711 | 0.335 |
4a | 268 (56.2) | 147 (58.57) | 121 (53.54) | ||
4b | 149 (31.2) | 72 (28.69) | 77 (34.07) | ||
4c | 27 (5.66) | 18 (7.17) | 9 (3.98) | ||
5 | 12 (2.52) | 6 (2.39) | 6 (2.66) | ||
6 | 2 (0.42) | 1 (0.39) | 1 (0.44) |
Multivariable risk factor for CLNM | β | SE | Wald | df | OR (95% CI) | P value |
---|---|---|---|---|---|---|
Age (< 45) | 1.218 | 0.192 | 40.260 | 1 | 3.380 (0.181–0.417) | < 0.01 |
Maximum diameter of thyroid nodules (< 10 mm) | 31.853 | 2 | ||||
10–20 mm | 0.801 | 0.204 | 15.435 | 1 | 2.228 (0.094–0.367) | < 0.01 |
> 20 mm | 1.568 | 0.303 | 26.712 | 1 | 4.795 (0.199–0.761) | < 0.01 |
Capsular invasion (no) | 0.410 | 0.186 | 4.882 | 1 | 1.507 (1.314–1.864) | 0.027 |
BRAF V600E gene mutation (no) | 1.858 | 0.312 | 35.505 | 1 | 6.410 (3.757–13.245) | < 0.01 |
Construction of the nomogram prediction model
Construction of the CNN prediction model
Training set | Test set | X2 | P -value | |||
---|---|---|---|---|---|---|
N | % | N | % | |||
Sex | ||||||
Male | 92 | 24.1% | 32 | 33.7% | 3.163 | 0.075 |
Female | 290 | 75.9% | 63 | 66.3% | ||
Age (years) | ||||||
< 45 | 184 | 48.2% | 50 | 52.6% | 0.441 | 0.507 |
≥ 45 | 198 | 51.8% | 45 | 47.4% | ||
Combined benign thyroid disease | ||||||
No | 209 | 54.7% | 48 | 50.5% | 2.126 | 0.547 |
Nodular goiter | 101 | 26.4% | 32 | 33.7% | ||
Lymphocytic thyroiditis | 55 | 14.4% | 11 | 11.6% | ||
Both | 17 | 4.5% | 4 | 4.2% | ||
BRAF V600E gene mutation | ||||||
No | 79 | 20.7% | 18 | 18.9% | 0.054 | 0.816 |
Yes | 303 | 79.3% | 77 | 81.1% | ||
Lymph node metastasis | ||||||
No | 201 | 52.6% | 50 | 52.6% | < 0.001 | 1.000 |
Yes | 181 | 47.4% | 45 | 47.4% | ||
Maximum diameter of thyroid nodules | ||||||
< 10 mm | 167 | 43.7% | 40 | 42.1% | 0.542 | 0.763 |
10–20 mm | 162 | 42.4 | 39 | 41.1% | ||
> 20 mm | 53 | 13.9% | 16 | 16.8% | ||
Nodule location | ||||||
Upper 1/3 | 79 | 20.7% | 19 | 20.0% | 1.573 | 0.814 |
Middle 1/3 | 118 | 30.9% | 27 | 28.4% | ||
Lower 1/3 | 63 | 16.5% | 13 | 13.7% | ||
Isthmus | 49 | 12.8% | 13 | 13.7% | ||
Whole | 73 | 19.1% | 23 | 24.2% | ||
Aspect Ratio | ||||||
< 1 | 230 | 60.2% | 44 | 46.3% | 5.453 | 0.020 |
≥ 1 | 152 | 39.8% | 51 | 53.7% | ||
Microcalcification | ||||||
No | 101 | 26.4% | 22 | 23.2% | 0.274 | 0.601 |
Yes | 281 | 73.6% | 73 | 76.8% | ||
Nodule boundary | ||||||
Clear | 158 | 41.4% | 34 | 35.8% | 0.764 | 0.382 |
Blurred | 224 | 58.6% | 61 | 64.2% | ||
Capsular invasion | ||||||
No | 218 | 57.1% | 50 | 52.6% | 5.020 | 0.081 |
Close | 55 | 14.4% | 8 | 8.4% | ||
Invasion | 109 | 28.5% | 37 | 38.9% | ||
Number of lesions | ||||||
Unifocal | 276 | 72.3% | 63 | 66.3% | 1.031 | 0.310 |
Multifocal | 106 | 27.7% | 32 | 33.7% |