Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. PD-L1 and PD-1 Tissue Expression and Plasma Levels Are Not Correlated with the Gender and Age of CCRCC Patients
2.2. The Expression of PD-L1 and PD-1 at the Tumour Centre and at the Infiltrating Front Is Correlated
2.3. Plasma PD-L1 Levels Are Lower in CCRCC Patients than in Control Subjects
2.4. Tissue Expression of PD-L1 and PD-1 as Well as Plasma sPD-L1 and sPD-1 Are Associated with CCRCC Aggressiveness
2.4.1. PD-L1 and PD-1 Expression Is Higher in High-Grade Tumors
2.4.2. PD-L1 and PD-1 Are Highly Expressed in CCRCC Tumors with Necrosis
2.4.3. PD-L1 and PD-1 Positive Staining Is More Frequent in Larger CCRCCs
2.4.4. PD-1 Expression Is Associated to Local Invasion (pT)
2.4.5. PD-L1 and PD-1 Tissue Expression and Plasma sPD-L1 and sPD-1 Are Higher in Patients with Synchronous Distant Metastasis
2.5. PD-L1 and PD-1 Expression and Plasma Levels in Terms of the Overall Survival (OS) of CCRCC Patients
2.6. PD-L1 and PD-1 Tissue Expression and Plasma Levels in Patients with Metastatic CCRCC According to IMDC Model and Response to Therapy
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. IMDC Model and MASS Response Criteria for Patients with Metastatic CCRCC
4.3. Immunohistochemistry
4.4. ELISA Assays
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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sPD-L1 (ng/mL) | sPD-1 (ng/mL) | ||||
---|---|---|---|---|---|
CCRCC | Controls | Mann-U (p=) | CCRCC | Controls | Mann-U (p=) |
902.8 ± 139.7 | 989.1 ± 155.9 | 0.048 | 1304.7 ± 306.3 | 941.3 ± 300.3 | 0.33 |
PD-L1 Expression at Tumour Centre | PD-L1 Expression at Infiltrating Front | |||||
Negative | Positive | Mann-U, p= | Negative | Positive | Mann-U, p= | |
Plasma sPD-L1 (ng/mL) | 849.1 ± 148.3 | 1182.1 ± 412.7 | 0.13 | 905.9 ± 184.5 | 1035.7 ± 353.1 | 0.99 |
PD-1 at Tumour Centre | PD-1 at Infiltrating Front | |||||
Negative | Positive | Mann-U, p= | Negative | Positive | Mann-U, p= | |
Plasma sPD-1 (ng/mL) | 1151.6 ± 344.4 | 1545.5 ± 576.5 | 0.61 | 1480.8 ± 446.6 | 983 ± 424.5 | 0.88 |
PD-L1 Expression in Both Areas | PD-1 Expression in Both Areas | |||||
Negative | Positive | Mann-U, p= | Negative | Positive | Mann-U, p= | |
Plasma sPD-L1 (ng/mL) | 845.1 ± 137.3 | 1439.5 ± 684.5 | 0.44 | - | - | - |
Plasma sPD-1 (ng/mL) | - | - | - | 1383.2 ± 367.4 | 1103 ± 562.6 | 0.94 |
CCRCC Patients | n= | sPD-L1 (ng/mL) | p= | sPD-1 (ng/mL) | p= |
---|---|---|---|---|---|
Fuhrman Grade | |||||
Low-Grade (G1-G2) | 49 | 982 ± 215 | 0.53 | 1795 ± 474 | 0.23 |
High-Grade (G3-G4) | 40 | 806 ± 168 | 678 ± 348 | ||
Necrosis | |||||
No | 63 | 754 ± 248 | 0.55 | 1472 ± 371 | 0.15 |
Yes | 26 | 964 ± 169 | 876 ± 537 | ||
Size | |||||
≤4 cm | 28 | 1143 ± 353 | 0.37 | 1880 ± 644 | 0.95 |
>4 to 7 cm | 39 | 685 ± 104 | 1021 ± 394 | ||
>7 cm | 22 | 982 ± 289 | 1024 ± 587 | ||
Local Invasion (pT) | |||||
pT1 | 59 | 896 ± 179 | 0.41 | 1467 ± 402 | 0.95 |
pT2 | 12 | 1049 ± 512 | 1414 ± 1089 | ||
pT3–pT4 | 18 | 826 ± 157 | 760 ± 364 | ||
Lymph node invasion (N) | |||||
No | 83 | 885 ± 148 | 0.08 | 1322 ± 328 | 0.14 |
Yes | 6 | 1148 ± 305 | 1089 ± 524 | ||
Distant metastasis (M) | |||||
No | 66 | 977 ± 184 | 1583 ± 395 | 0.14 c | |
Synchronous | 10 | 1014 ± 191 | 0.034 a,b | 824 ± 369 | |
Metachronous | 13 | 438 ± 76 | 130 ± 68 |
Tumour Centre | Centre-Front | Plasma | |||||||||||
5-Year OS | Variables | p | ExpB | CI | p | ExpB | CI | p | ExpB | CI | |||
pT | 0.04 | 1.9 | 1 | 3.5 | 0.09 | 1.65 | 0.92 | 9 | 0.004 | 2.24 | 1.3 | 3.86 | |
N | 0.02 | 4.09 | 1.2 | 13.9 | 0.001 | 6.68 | 2.1 | 21.4 | - | ||||
M | 0.01 | 2 | 1.19 | 3.38 | 0.005 | 2.07 | 1.24 | 3.46 | 8 × 10−6 | 2.83 | 1.68 | 4.75 | |
PD-L1 | 0.06 | 2.74 | 0.96 | 7.78 | 0.026 | 3.34 | 1.15 | 9.66 | 1 × 10−5 | 8.67 | 3.26 | 23.1 | |
Tumour Centre and Plasma | Front and Plasma | Centre-Front and Plasma | |||||||||||
5-Year OS | Variables | p | ExpB | CI | p | ExpB | CI | p | ExpB | CI | |||
pT | 0.002 | 4.66 | 1.77 | 12.22 | 0.01 | 1.83 | 1.34 | 9.12 | 0.017 | 3.3 | 1.24 | 8.66 | |
N | 0.02 | 4.29 | 1.21 | 15.17 | 0.002 | 3.28 | 1.96 | 21.7 | 0.005 | 5.85 | 1.69 | 20.2 | |
M | 0.001 | 2.33 | 1.4 | 3.89 | 0.0001 | 5.13 | 1.6 | 4.5 | 0.0001 | 2.63 | 1.57 | 4.4 | |
PD-L1c | 0.03 | 3.5 | 1.09 | 11.28 | 0.009 | 2.56 | 1.53 | 19.7 | 0.003 | 7.98 | 2.05 | 31 |
Tumor Centre | Tumor Front | Plasma | ||||||
PD-L1 n (%) | PD-L1 n (%) | sPD-L1 (ng/mL) | ||||||
Variables | Negative | Positive | Total | Negative | Positive | Total | ||
IMDC score | Favorable | 7 (77.8) | 2 (22.2) | 9 | 3 (42.9) | 4 (52.1) | 7 | 488 ± 112.9 |
Intermediate | 6 (75) | 2 (25) | 8 | 5 (71.4) | 2 (28.6) | 7 | 705.4 ± 259.4 | |
Poor | 2 (33.3) | 4 (66.7) | 6 | 1 (20) | 4 (80) | 5 | 967 ± 135.4 | |
Total | 15 | 8 | 23 | 9 | 10 | 19 | 688.6 ± 109.5 | |
p = 0.161/p = 0.056 * | p = 0.203 | p = 0.062/p = 0.021 * | ||||||
Tumor Center | Tumor Front | Plasma | ||||||
PD-1 n (%) | PD-1 n (%) | sPD-1 (ng/mL) | ||||||
Variables | Negative | Positive | Total | Negative | Positive | Total | ||
IMDC score | Favorable | 5 (55.6) | 4 (44.4) | 9 | 3 (33.3) | 6 (66.7) | 9 | 154.3 ± 93 |
Intermediate | 3 (37.5) | 5 (62.5) | 8 | 2 (28.6) | 5 (71.4) | 7 | 618.1 ± 294.8 | |
Poor | 2 (33.3) | 4 (66.7) | 6 | 3 (50) | 3 (50) | 6 | 650 ± 532.3 | |
Total | 15 | 8 | 23 | 8 | 14 | 22 | 442.1 ± 182.8 | |
p = 0.637 | p = 0.704 | p = 0.341 |
Tumour Centre | Tumour Front | Plasma | ||||||
PD-L1 n (%) | PD-L1 n (%) | sPD-L1 (ng/mL) | ||||||
Variables | Negative | Positive | Total | Negative | Positive | Total | ||
MASS Response | Favorable | 6 (60) | 4 (40) | 10 | 2 (28.6) | 5 (71.4) | 7 | 387.5 ± 89.1 |
Indeterminate | 2 (66.7) | 1 (33.3) | 3 | 2 (66.7) | 1 (33.3) | 3 | 811.4 ± 78.1 | |
Unfavorable | 2 (66.7) | 1 (33.3) | 3 | 2 (100) | 0 (0) | 2 | 1621 ± 442.9 | |
Total | 10 | 6 | 16 | 6 | 6 | 12 | 698.3 ± 151.2 | |
p = 0.965 | p = 0.164/p = 0.079 ** | p = 0.014/p = 0.021 */p = 0.005 ** | ||||||
Tumour Centre | Tumour Front | Plasma | ||||||
PD-1 n (%) | PD-1 n (%) | sPD-1 (ng/mL) | ||||||
Variables | Negative | Positive | Total | Negative | Positive | Total | ||
MASS Response | Favorable | 5 (50) | 5 (50) | 10 | 3 (33.3) | 6 (66.7) | 9 | 268.9 ± 129.9 |
Indeterminate | 2 (66.7) | 1 (33.3) | 3 | 1 (33.3) | 2 (66.7) | 3 | 433.1 ± 265.7 | |
Unfavorable | 1 (33.3) | 3 (66.7) | 3 | 3 (100) | 0 (0) | 3 | 1743.6 ± 935.1 | |
Total | 8 | 8 | 16 | 7 | 8 | 15 | 647.1 ± 267 | |
p = 0.717 | p = 0.117 | p = 0.33 |
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Larrinaga, G.; Solano-Iturri, J.D.; Errarte, P.; Unda, M.; Loizaga-Iriarte, A.; Pérez-Fernández, A.; Echevarría, E.; Asumendi, A.; Manini, C.; Angulo, J.C.; et al. Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma. Cancers 2021, 13, 667. https://doi.org/10.3390/cancers13040667
Larrinaga G, Solano-Iturri JD, Errarte P, Unda M, Loizaga-Iriarte A, Pérez-Fernández A, Echevarría E, Asumendi A, Manini C, Angulo JC, et al. Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma. Cancers. 2021; 13(4):667. https://doi.org/10.3390/cancers13040667
Chicago/Turabian StyleLarrinaga, Gorka, Jon Danel Solano-Iturri, Peio Errarte, Miguel Unda, Ana Loizaga-Iriarte, Amparo Pérez-Fernández, Enrique Echevarría, Aintzane Asumendi, Claudia Manini, Javier C. Angulo, and et al. 2021. "Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma" Cancers 13, no. 4: 667. https://doi.org/10.3390/cancers13040667
APA StyleLarrinaga, G., Solano-Iturri, J. D., Errarte, P., Unda, M., Loizaga-Iriarte, A., Pérez-Fernández, A., Echevarría, E., Asumendi, A., Manini, C., Angulo, J. C., & López, J. I. (2021). Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma. Cancers, 13(4), 667. https://doi.org/10.3390/cancers13040667