Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Tissue Specimens
2.2. IHC Staining and Evaluation in UrC
2.3. Statistical Analysis
3. Results
3.1. Clinicopathological Features of Urachal Carcinoma
3.2. Quantity Pattern of Immune Cells in Urachal Carcinoma
3.3. Associations between Immune Characteristics and Clinicopathological Features in Urachal Carcinoma
3.4. Associations between Immune Cell PD-L1 Expression and Clinicopathological Features and Immune Characteristics in Urachal Carcinoma
3.5. Association between CD8+ T Cell Density and PD-L1 or PD1 Expression on Immune Cells in Urachal Carcinoma
3.6. PD-L1 and PD1 Expression and Immune Cells Densities Can Predict OS and DFS in Urachal Carcinomas
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Intratumoral Immune Characteristics (Cells/mm2) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N | CD20 | p Value | CD3 | p Value | CD 4 | p Value | CD 8 | p Value | FOXP3 | p Value | CD 68 | p Value | HLA-DR | p Value | CD163 | p Value | |
Gender | 0.3615 | 0.3525 | 0.3325 | 0.3275 | 0.4658 | 0.9666 | 0.2176 | 0.5293 | |||||||||
Female | 9 | 19.69 | 73.31 | 37.24 | 35.58 | 29.60 | 19.82 | 36.22 | 16.24 | ||||||||
Male | 28 | 27.74 | 97.68 | 28.38 | 51.53 | 39.01 | 20.17 | 56.53 | 19.96 | ||||||||
Age (a) | 0.5668 | 0.6604 | 0.2749 | 0.7518 | 0.8497 | 0.1799 | 0.9187 | 0.6375 | |||||||||
≤51 | 20 | 23.87 | 85.76 | 27.46 | 47.58 | 36.70 | 24.27 | 52.95 | 18.82 | ||||||||
>51 | 17 | 28.29 | 95.27 | 36.06 | 43.32 | 34.68 | 15.39 | 51.55 | 21.20 | ||||||||
Tumor size (b) | 0.9702 | 0.4933 | 0.9194 | 0.4649 | 0.5982 | 0.1971 | 0.1251 | 0.0722 | |||||||||
≤4 cm | 20 | 25.77 | 83.33 | 31.78 | 41.11 | 33.20 | 16.26 | 42.82 | 15.83 | ||||||||
>4 cm | 17 | 26.06 | 98.13 | 30.98 | 50.93 | 38.80 | 24.81 | 63.47 | 24.72 | ||||||||
Vascular invasion | 0.9589 | 0.5833 | 0.8441 | 0.2302 | 0.3313 | 0.0611 | 0.2367 | 0.6254 | |||||||||
No | 30 | 25.81 | 82.87 | 31.79 | 41.77 | 33.30 | 17.24 | 48.45 | 19.32 | ||||||||
Yes | 7 | 26.31 | 102.4 | 29.80 | 62.14 | 46.37 | 32.83 | 68.86 | 22.46 | ||||||||
Perineural invasion | 0.3691 | 0.2339 | 0.1316 | 0.4042 | 0.0532 | 0.2422 | 0.1397 | 0.5096 | |||||||||
No | 21 | 22.90 | 79.02 | 26.29 | 40.75 | 27.06 | 16.81 | 43.65 | 18.47 | ||||||||
Yes | 16 | 29.85 | 104.7 | 38.14 | 52.01 | 47.21 | 24.63 | 63.68 | 21.18 | ||||||||
Mayo stage | 0.2493 | 0.4169 | 0.6842 | 0.1949 | 0.5363 | 0.1201 | 0.0027 | 0.0779 | |||||||||
II | 6 | 21.90 | 63.37 | 27.27 | 29.57 | 23.07 | 15.77 | 42.07 | 21.08 | ||||||||
III | 23 | 22.57 | 90.18 | 30.32 | 42.51 | 36.99 | 18.15 | 40.61 | 16.03 | ||||||||
IV | 8 | 37.90 | 110.1 | 37.65 | 6.60 | 41.80 | 29.38 | 93.63 | 29.68 | ||||||||
Histological type | 0.8698 | 0.9488 | 0.0826 | 0.2879 | 0.1256 | 0.5743 | 0.3572 | ||||||||||
Enteric | 14 | 25.76 | 98.96 | 33.77 | 55.41 | 39.97 | 23.86 | 50.46 | 21.50 | ||||||||
Mucinous | 7 | 21.97 | 52.00 | 13.89 | 23.97 | 18.63 | 6.429 | 39.94 | 12.49 | ||||||||
Mixed | 16 | 27.83 | 99.09 | 37.01 | 46.53 | 39.60 | 23.00 | 59.34 | 21.78 | ||||||||
Relapse | 0.4716 | 0.1308 | 0.8501 | 0.1904 | 0.1134 | 0.4015 | 0.1016 | 0.9248 | |||||||||
No | 9 | 21.02 | 62.31 | 29.69 | 30.29 | 21.22 | 15.27 | 32.98 | 20.33 | ||||||||
Yes | 28 | 27.47 | 99.01 | 31.96 | 50.55 | 40.145 | 21.77 | 58.52 | 19.78 | ||||||||
MMR status (c) | 0.5048 | 0.4016 | 0.8173 | 0.4978 | 0.1047 | 0.8180 | 0.9800 | 0.7490 | |||||||||
pMMR | 34 | 26.66 | 92.78 | 31.68 | 46.97 | 38.28 | 20.42 | 52.36 | 20.15 | ||||||||
dMMR | 3 | 17.27 | 60.07 | 28.33 | 30.33 | 7.333 | 17.60 | 51.73 | 17.20 |
Variables | Peritumoral Immune Characteristics (Cells/mm2) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N | CD20 | p Value | CD3 | p Value | CD 4 | p Value | CD 8 | p Value | FOXP3 | p Value | CD 68 | p Value | HLA-DR | p Value | CD163 | p Value | |
Gender | 0.4772 | 0.6944 | 0.8820 | 0.8028 | 0.5933 | 0.5357 | 0.3430 | 0.7074 | |||||||||
Female | 9 | 53.29 | 92.38 | 45.00 | 54.64 | 23.36 | 14.87 | 68.71 | 15.84 | ||||||||
Male | 28 | 69.80 | 100.8 | 46.99 | 58.13 | 28.35 | 12.27 | 88.32 | 18.32 | ||||||||
Age (a) | 0.7648 | 0.4899 | 0.2456 | 0.7843 | 0.1532 | 0.4394 | 0.3557 | 0.1000 | |||||||||
≤51 | 20 | 67.49 | 105.5 | 21.91 | 55.24 | 31.53 | 13.20 | 91.52 | 15.27 | ||||||||
>51 | 17 | 61.71 | 93.39 | 39.53 | 58.46 | 20.47 | 17.47 | 75.75 | 27.60 | ||||||||
Tumor size (b) | 0.3094 | 0.6421 | 0.5250 | 0.5004 | 0.8135 | 0.3181 | 0.8818 | 0.5086 | |||||||||
≤4cm | 20 | 73.80 | 103.7 | 47.25 | 60.35 | 27.30 | 12.63 | 83.10 | 18.62 | ||||||||
>4cm | 17 | 54.28 | 95.44 | 44.84 | 52.45 | 25.45 | 18.14 | 85.65 | 23.66 | ||||||||
Vascular invasion | 0.5180 | 0.9274 | 0.3129 | 0.3571 | 0.8195 | 0.2606 | 0.2503 | 0..2391 | |||||||||
No | 30 | 67.83 | 99.53 | 43.51 | 54.13 | 26.88 | 16.65 | 88.98 | 23.07 | ||||||||
Yes | 7 | 51.97 | 101.6 | 57.43 | 67.83 | 24.60 | 8.771 | 64.10 | 11.74 | ||||||||
Perineural invasion | 0.5953 | 0.1594 | 0.0447 | 0.0752 | 0.1600 | 0.7878 | 0.3843 | 0.9357 | |||||||||
No | 21 | 60.37 | 89.13 | 36.88 | 47.82 | 21.71 | 14.51 | 77.81 | 20.67 | ||||||||
Yes | 16 | 70.69 | 114.1 | 58.30 | 68.40 | 32.66 | 16.01 | 92.76 | 21.29 | ||||||||
Mayo stage | 0.7321 | 0.4896 | 0.4054 | 0.2331 | 0.7579 | 0.5021 | 0.6917 | 0.1014 | |||||||||
II | 6 | 48.71 | 76.47 | 34.07 | 41.83 | 22.27 | 22.50 | 69.70 | 33.67 | ||||||||
III | 23 | 66.69 | 102.9 | 45.28 | 54.84 | 28.71 | 13.57 | 89.43 | 17.26 | ||||||||
IV | 8 | 72.00 | 109.1 | 57.68 | 73.28 | 23.08 | 14.32 | 80.39 | 20.93 | ||||||||
Histological type | 0.1502 | 0.6711 | 0.1870 | 0.1086 | 0.2672 | 0.0458 | 0.5277 | 0.1014 | |||||||||
Enteric | 14 | 86.00 | 109.9 | 44.64 | 71.86 | 34.33 | 23.36 | 96.40 | 31.10 | ||||||||
Mucinous | 7 | 67.49 | 90.43 | 28.40 | 42.91 | 24.71 | 6.871 | 80.60 | 15.60 | ||||||||
Mixed | 16 | 45.15 | 95.36 | 55.21 | 49.51 | 20.55 | 11.61 | 75.27 | 14.38 | ||||||||
Relapse | 0.2220 | 0.0303 | 0.2639 | 0.0407 | 0.2287 | 0.1748 | 0.3044 | 0.6097 | |||||||||
No | 9 | 44.29 | 67.00 | 35.51 | 36.18 | 18.22 | 8.622 | 68.89 | 17.51 | ||||||||
Yes | 28 | 71.44 | 110.5 | 49.56 | 63.32 | 29.09 | 17.62 | 89.22 | 22.04 | ||||||||
MMR status (c) | 0.7228 | 0.5314 | 0.6937 | 0.8005 | 0.1324 | 0.9010 | 0.9762 | 0.9256 | |||||||||
pMMR | 34 | 63.82 | 101.6 | 46.78 | 57.16 | 28.17 | 15.26 | 84.20 | 20.83 | ||||||||
dMMR | 3 | 76.33 | 81.20 | 38.99 | 51.73 | 6.933 | 14.00 | 85.13 | 22.13 |
Variables (Mean) | PD-L1 Expression in Immune Cells | |||
---|---|---|---|---|
Negative | Positive | t-Test | p Value | |
CD20 density (cells/mm2) | ||||
Intratumor | 21.66 | 33.74 | 1.557 | 0.1286 |
Peritumor | 69.55 | 56.12 | 0.6740 | 0.5048 |
CD3 density (cells/mm2) | ||||
Intratumor | 67.04 | 132.8 | 3.365 | 0.0019 |
Peritumor | 85.88 | 125.8 | 2.315 | 0.0266 |
Intraepithelial | 3.525 | 4.615 | 0.3888 | 0.6998 |
CD4 density (cells/mm2) | ||||
Intratumor | 23.91 | 45.26 | 2.885 | 0.0067 |
Peritumor | 35.83 | 65.18 | 2.886 | 0.0066 |
Intraepithelial | 0.1583 | 0.3538 | 0.5814 | 0.5646 |
CD8 density (cells/mm2) | ||||
Intratumor | 33.63 | 67.77 | 2.682 | 0.0111 |
Peritumor | 50.53 | 68.14 | 1.489 | 0.1485 |
Intraepithelial | 2.825 | 3.692 | 0.3728 | 0.7115 |
FOXP3 density (cells/mm2) | ||||
Intratumor | 24.30 | 56.95 | 3.417 | 0.0016 |
Peritumor | 23.77 | 31.40 | 0.9493 | 0.3490 |
CD68 density (cells/mm2) | ||||
Intratumor | 16.13 | 27.69 | 1.733 | 0.0919 |
Peritumor | 13.72 | 17.82 | 0.7164 | 0.4785 |
HLA-DR (a) density (cells/mm2) | ||||
Intratumor | 45.29 | 65.26 | 1.448 | 0.1564 |
Peritumor | 86.43 | 80.29 | 0.3454 | 0.7319 |
CD163 density (cells/mm2) | ||||
Intratumor | 18.84 | 21.89 | 0.5846 | 0.5626 |
Peritumor | 18.78 | 24.91 | 0.7796 | 0.4409 |
The proportion of PD1 expression (%) | ||||
Intratumor | 1.208 | 6.462 | 2.646 | 0.0121 |
Peritumor | 5.000 | 7.692 | 1.453 | 0.1550 |
TLS (b) | ||||
The number of per slide | 1.453 | 0.4856 | 2.907 | 0.0063 |
Variables | PD-L1 Expression in Immune Cells | |||
---|---|---|---|---|
N | Negative | Positive | p Value | |
Gender | 0.8964 | |||
Female | 9 | 6(66.67%) | 3(33.33%) | |
Male | 28 | 18(64.29%) | 10(35.71%) | |
Age (a) | 0.4779 | |||
≤51 | 20 | 14(70.00%) | 6(30.00%) | |
>51 | 17 | 10(58.82%) | 7(41.18%) | |
Tumor size (b) | 0.9851 | |||
≤4 cm | 20 | 13(65.00%) | 7(35.00%) | |
>4 cm | 17 | 11(64.71%) | 6(35.29%) | |
Vascular invasion | 0.1756 | |||
No | 30 | 21(70.00%) | 9(30.00%) | |
Yes | 7 | 3(42.86%) | 4(57.14%) | |
Perineural invasion | 0.6657 | |||
No | 21 | 13(61.90%) | 8(38.10%) | |
Yes | 16 | 11(68.75%) | 5(31.25%) | |
Histological type | 0.2420 | |||
Enteric | 14 | 11(53.6%) | 3(46.4%) | |
Mucinous | 7 | 5(71.43%) | 2(28.57%) | |
Mixed | 16 | 8(50.00%) | 8(50.00%) | |
Mayo stage | 0.6044 | |||
II | 6 | 4(66.67%) | 2(33.33%) | |
III | 23 | 16(69.57%) | 7(30.43%) | |
IV | 8 | 4(50.00%) | 4(50.00%) | |
Relapse | 0.8964 | |||
No | 9 | 6(66.67%) | 3(33.33%) | |
Yes | 28 | 18(64.29%) | 10(35.71%) | |
MMR status (c) | 0.9456 | |||
pMMR | 34 | 22(64.71%) | 12(35.29%) | |
dMMR | 3 | 2(66.67%) | 1(33.33%) | |
Therapeutic efficacy | 0.7829 | |||
SD | 7 | 4(57.14%) | 3(42.86%) | |
PD | 11 | 7(63.64%) | 4(36.36%) |
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Zhang, X.; Wang, S.; Nie, R.-C.; Qu, C.; Chen, J.; Yang, Y.; Cai, M. Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy. Cancers 2022, 14, 615. https://doi.org/10.3390/cancers14030615
Zhang X, Wang S, Nie R-C, Qu C, Chen J, Yang Y, Cai M. Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy. Cancers. 2022; 14(3):615. https://doi.org/10.3390/cancers14030615
Chicago/Turabian StyleZhang, Xinke, Suijing Wang, Run-Cong Nie, Chunhua Qu, Jierong Chen, Yuanzhong Yang, and Muyan Cai. 2022. "Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy" Cancers 14, no. 3: 615. https://doi.org/10.3390/cancers14030615