Introduction
Materials and methods
Patients and samples
Data analysis
Results
Baseline characteristics of included patients
Paired (N = 83) | Metastatic (N = 80) | P value | |
---|---|---|---|
Age, n (%) | 0.546 | ||
< 70 | 76 (91.6) | 71 (88.8) | |
≥ 70 | 7 (8.4) | 9 (11.2) | |
Gender, n (%) | 0.873 | ||
Male | 54 (65.1) | 53 (66.3) | |
Female | 29 (34.9) | 27 (33.7) | |
ISUP, n (%) | 0.066 | ||
< 4 | 49 (67.1) | 58 (80.6) | |
≥ 4 | 24 (32.9) | 14 (19.4) | |
Histological Type, n (%) | 0.032 | ||
ccRCC | 59 (71.1) | 68 (61.3) | |
Non-ccRCC | 24 (28.9) | 12 (38.7) | |
Pathology, n (%) | |||
Sarcomatoid | 6 (19.4) | 2 (28.6) | 0.509 |
Necrosis | 25 (80.6) | 5 (71.4) | 0.491 |
Nephrectomy, n (%) | 0.001 | ||
Yes | 80 (96.4) | 57 (77.0) | |
No | 3 (3.6) | 17 (23.0) | |
ECOG, n (%) | 0.801 | ||
0–1 | 53 (70.7) | 59 (76.6) | |
≥ 2 | 22 (29.3) | 18 (23.4) | |
IMDC, n (%) | 0.293 | ||
Low | 14 (18.3) | 19 (28.4) | |
Intermediate | 43 (57.3) | 37 (55.2) | |
High | 18 (24.0) | 11 (16.4) | |
T stage, n (%) | 0.587 | ||
< 2b | 46 (59.7) | 12 (66.7) | |
≥ 2b | 31 (40.3) | 6 (33.3) | |
Metastasis, n (%) | |||
Lung | 6 (8.1) | 17 (28.8) | 0.010 |
Brain | 7 (9.5) | 12 (20.3) | 0.192 |
Liver | 1 (1.4) | 2 (3.4) | 0.539 |
Bone | 18 (24.3) | 22 (37.3) | 0.389 |
Lymph node | 42 (56.8) | 6 (10.2) | 0.001 |
Treatment, n (%) | |||
Cytokine | 14 (16.9) | 8 (10.0) | 0.345 |
Target therapy | 34 (41.0) | 30 (37.5) | 0.882 |
Radiotherapy | 7 (8.4) | 7 (8.8) | 0.673 |
Chemotherapy | 3 (3.6) | 5 (6.2) | 0.360 |
Unknown | 25 (30.1) | 30 (37.5) |
Expressions of TIM-3 in the whole and paired cohort
TIM-3 | P value | ||
---|---|---|---|
Positive | Negative | ||
Total | 92 (56.4) | 71 (43.6) | |
Age, n (%) | 0.987 | ||
< 70y | 83 (90.2) | 64 (90.1) | |
≥ 70y | 9 (9.8) | 7 (9.9) | |
Gender, n (%) | 0.259 | ||
Male | 57 (53.3) | 50 (46.7) | |
Female | 35 (62.5) | 21 (37.5) | |
ISUP, n (%) | 0.055 | ||
< 4 | 67 (79.8) | 40 (65.6) | |
≥ 4 | 17 (20.2) | 21 (34.4) | |
Histological Type, n(%) | 0.377 | ||
ccRCC | 74 (58.3) | 53 (41.7) | |
Non-ccRCC | 18 (50.0) | 18 (50.0) | |
Pathology, n (%) | |||
Sarcoma | 5 (62.5) | 3 (37.5) | 0.898 |
Necrosis | 20 (66.7) | 10 (33.3) | 0.958 |
Nephrectomy | 0.026 | ||
Yes | 84 (61.3) | 53 (38.7) | |
No | 7 (35.0) | 13 (65.0) | |
ECOG, n (%) | 0.239 | ||
0–1 | 68 (60.7) | 44 (39.3) | |
≥ 2 | 20 (50.0) | 20 (50.0) | |
IMDC, n (%) | 0.030 | ||
Low | 23 (69.7) | 10 (30.3) | |
Intermediate | 49 (61.3) | 31 (38.7) | |
High | 11 (37.9) | 18 (62.1) | |
T stage, n (%) | 0.391 | ||
< 2b | 38 (64.4) | 20 (55.6) | |
≥ 2b | 21 (35.6) | 16 (44.4) | |
Treatment, n (%) | |||
Cytokine | 12 (54.5) | 10 (45.5) | 0.762 |
Targeted therapy | 32 (50.0) | 32 (50.0) | 0.088 |
Radiotherapy | 7 (50.0) | 7 (50.0) | 0.504 |
Chemotherapy | 5 (62.5) | 3 (37.5) | 0.817 |
TIM-3, N(%) | P value | |||
---|---|---|---|---|
N | Positive | Negative | ||
Primary | 83 | 44 (53.0) | 39 (47.0) | |
Metastasisa | 163 | |||
Total | 175 | 79 (45.4) | 95 (54.6) | 0.253 |
Lung/lymph node | 72 | 32 (44.4) | 40 (55.6) | 0.287 |
Lung | 24 | 12 (50.0) | 12 (50.0) | 0.795 |
Lymph node | 46 | 20 (43.5) | 26 (56.5) | 0.300 |
Bone | 41 | 16 (39.0) | 25 (61.0) | 0.143 |
Brain | 19 | 8 (42.1) | 11 (57.9) | 0.391 |
Viscera without lung | 14 | 11 (78.6) | 3 (21.4) | 0.074 |
Ipsilateral Adrenal gland | 4 | 3 (75.0) | 1 (25.0) | 0.389 |
Others | 20 | 7 (35.0) | 13 (65.0) | 0.148 |
Associations of TIM-3 expression with clinical outcomes
Multivariate analysis of PFS and OS in the whole, paired and targeted cohort
Cox’s regression for PFS | Cox’s regression for OS | |||||
---|---|---|---|---|---|---|
HR | 95% Cl | P value | HR | 95% Cl | P value | |
Gender | ||||||
Male vs < female | 0.800 | 0.362–1.769 | 0.581 | 0.707 | 0.288–1.739 | 0.450 |
Age | ||||||
≥ 70 vs < 70 | 1.755 | 0.341–9.044 | 0.501 | 0.698 | 0.200–2.430 | 0.572 |
ISUP | ||||||
≥ 4 vs < 4 | 1.423 | 0.632–3.204 | 0.394 | 2.214 | 0.968–5.063 | 0.060 |
Nephrectomy | ||||||
Yes vs No | 0.544 | 0.190–1.557 | 0.257 | 0.273 | 0.101–0.735 | 0.010 |
IMDC | ||||||
Low | 0.956 | Ref. | Ref. | 0.284 | ||
Intermediate | 1.067 | 0.374–3.040 | 0.904 | 0.396 | 0.123–1.276 | 0.121 |
High | 1.186 | 0.362–3.891 | 0.778 | 0.539 | 0.159–1.832 | 0.322 |
T stage | ||||||
≥ T2b vs < T2b | 1.512 | 0.688–3.319 | 0.303 | – | – | – |
CHOL (mmol/L) | ||||||
≥ 5 vs < 5 | 0.517 | 0.144–1.858 | 0.312 | 0.463 | 0.113–1.903 | 0.286 |
HDLC (mmol/L) | ||||||
≥ 5 vs < 5 | – | – | – | 0.781 | 0.363–1.681 | 0.528 |
LDH (IU/L) | ||||||
≥ 175 vs < 175 | 1.877 | 0.918–3.837 | 0.084 | 3.004 | 1.272–7.098 | 0.012 |
Na (mmol/L) | ||||||
≥ 137 vs < 137 | 8.458 | 1.909–37.468 | 0.005 | 18.993 | 3.629–99.415 | 0.001 |
Full model without TIM-3 | ||||||
PA | 0.747 | 0.781 | ||||
Full model with TIM-3(P or M*) | ||||||
TIM-3 | 0.669 | 0.278–1.605 | 0.367 | 0.536 | 0.245–1.172 | 0.118 |
PA | 0.73 | 0.775 | ||||
Full model with TIM-3(M#) | ||||||
TIM-3(M) | 0.377 | 0.162–0.876 | 0.023 | 0.351 | 0.156–0.787 | 0.011 |
PA | 0.756 | 0.811 |
Cox’s regression for PFS | Cox’s regression for OS | |||||
---|---|---|---|---|---|---|
HR | 95% Cl | P value | HR | 95% Cl | P value | |
Age | ||||||
≥ 70 vs < 70 | 1.996 | 0.218–18.285 | 0.541 | 1.825 | 0.262–12.725 | 0.544 |
ISUP | ||||||
≥ 4 vs < 4 | 1.038 | 0.416–2.587 | 0.937 | 0.993 | 0.379–2.602 | 0.989 |
Nephrectomy | ||||||
Yes vs No | – | – | – | 0.663 | 0.126–3.485 | 0.628 |
IMDC | ||||||
Low | Ref. | Ref. | 0.451 | Ref. | Ref. | 0.794 |
Intermediate | 1.242 | 0.443–3.480 | 0.680 | 0.704 | 0.214–2.317 | 0.564 |
High | 1.965 | 0.630–6.134 | 0.245 | 0.672 | 0.195–2.317 | 0.529 |
T stage | ||||||
≥ 2b vs < 2b | 1.565 | 0.714–3.432 | 0.264 | – | – | – |
ALP (IU/L) | ||||||
≥ 74 vs < 74 | – | – | – | 2.477 | 0.661–9.279 | 0.178 |
LDH (IU/L) | ||||||
≥ 175 vs < 175 | 1.697 | 0.720–4.000 | 0.227 | 3.043 | 0.998–9.278 | 0.050 |
Na (mmol/L) | ||||||
≥ 137 vs < 137 | – | – | – | 15.965 | 1.864–136.722 | 0.011 |
Full model without TIM-3 | ||||||
PA | 0.713 | 0.78 | ||||
Full model with TIM-3(P or M*) | ||||||
TIM-3(P or M) | 1.277 | 0.489–3.332 | 0.617 | 0.631 | 0.241–1.652 | 0.348 |
PA | 0.715 | 0.782 | ||||
Full model with TIM-3(P#) | ||||||
TIM-3(P) | 0.953 | 0.413–2.2 | 0.911 | 0.594 | 0.237–1.486 | 0.265 |
PA | 0.692 | 0.783 | ||||
Full model with TIM-3(M§) | ||||||
TIM-3(M) | 0.47 | 0.194–1.138 | 0.094 | 0.239 | 0.087–0.661 | 0.006 |
PA | 0.745 | 0.81 |
Cox’s regression for PFS | Cox’s regression for OS | |||||
---|---|---|---|---|---|---|
HR | 95% Cl | P value | HR | 95% Cl | P value | |
ISUP | ||||||
≥ 4 vs < 4 | 1.082 | 0.363–3.232 | 0.887 | 1.826 | 0.611–5.456 | 0.281 |
Nephrectomy | ||||||
Yes vs No | 0.081 | 0.016–0.408 | 0.002 | 0.066 | 0.014–0.299 | < 0.001 |
ECOG | ||||||
≥ 2 vs < 2 | 1.131 | 0.382–3.345 | 0.825 | 1.566 | 0.428–5.721 | 0.498 |
IMDC | ||||||
Low | 1 | Ref. | 0.860 | 1 | Ref. | 0.108 |
Intermediate | 1.195 | 0.300–4.760 | 0.800 | 0.302 | 0.055–1.646 | 0.166 |
High | 1.590 | 0.283–8.938 | 0.599 | 1.525 | 0.268–8.664 | 0.634 |
Time from diagnosis to metastasis | ||||||
Synchronous vs Metachronous | 0.534 | 0.186–1.535 | 0.244 | – | – | – |
T stage | – | – | – | |||
≥ 2b vs <2b | 3.438 | 0.990–11.937 | 0.052 | – | – | – |
ALP (IU/L) | ||||||
≥ 78 vs < 78 | – | – | – | 1.018 | 1.003–1.034 | 0.021 |
Na (mmol/L) | ||||||
< 137 vs ≥137 | 18.258 | 1.506–221.386 | 0.023 | 0.999 | 0.997–1.001 | 0.336 |
Full model without TIM-3 | ||||||
PA | 0.735 | 0.842 | ||||
Full model with TIM-3(P or M*) | ||||||
TIM-3(P or M) | 0.456 | 0.147–1.416 | 0.174 | 0.755 | 0.296–1.926 | 0.556 |
PA | 0.738 | 0.844 | ||||
Full model with TIM-3(M#) | ||||||
TIM-3(M) | 0.167 | 0.048–0.586 | 0.005 | 0.537 | 0.226–1.277 | 0.159 |
PA | 0.791 | 0.873 |