CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Information
2.2. Multiplex Immunohistochemistry (mIHC) Test
2.3. Random Grouping and Determination of Optimal Cut-Off Values
2.4. Construction and Validation of the Nomogram
2.5. Risk Stratification
2.6. Differential Gene Expression Analysis
2.7. Immune Infiltration in the TME
2.8. Statistical Analysis
3. Results
3.1. Differences in the Expression of CD39 in ESCC Cancer and Paracancerous Tissues
3.2. Clinical Characteristics of 95 ESCC Patients
3.3. Optimal Cut-Off Values and Cox Regression Analysis of the Training Group
3.4. Nomogram Construction
3.5. Nomogram Validation
3.6. Risk Stratification
3.7. Differential Expression of ENTPD1 between ESCC and Normal Tissues
3.8. Association of ENTPD1 Expression with Immune Infiltration in TME of Esophageal Carcinoma
4. Discussion
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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Variables | Training Group | Validation Group | p-Value a |
---|---|---|---|
Number | 67 | 28 | |
Age, mean ± SD, months | 65.91 ± 9.12 | 66.43 ± 8.23 | 0.79 |
Tumor length, mean ± SD, cm | 4.66 ± 1.79 | 5.06 ± 1.74 | 0.22 |
Tumor volume, mean ± SD, cm3 | 21.18 ± 17.91 | 26.63 ± 27.16 | 0.52 |
Proportion of positive lymph nodes, mean ± SD, % | 15.68 ± 24.61 | 13.93 ± 16.17 | 0.46 |
CD39+ count, mean ± SD | 4014.48 ± 2957.20 | 3559.89 ± 2393.59 | 0.68 |
CD8+ count, mean ± SD | 277.79 ± 418.32 | 278.93 ± 395.91 | 0.32 |
CD39-expressing CD8+ T cells, mean ± SD, % | 50.53 ± 21.50 | 46.70 ± 21.83 | 0.44 |
CD39+ in CK+ region, mean ± SD | 831.16 ± 753.49 | 1191.30 ± 1201.52 | 0.20 |
CD39+ in CK− region, mean ± SD | 3183.31 ± 2786.14 | 2368.59 ± 1707.59 | 0.35 |
CD8+ in CK+ region, mean ± SD | 45.93 ± 101.88 | 79.81 ± 200.42 | 0.44 |
CD8+ in CK− region, mean ± SD | 231.87 ± 335.91 | 199.11 ± 231.87 | 0.49 |
CD39-expressing CD8+ T cells in CK+ region, mean ± SD, % | 36.06 ± 28.32 | 26.21 ± 25.31 | 0.11 |
CD39-expressing CD8+ T cells in CK− region, mean ± SD, % | 56.58 ± 24.80 | 55.14 ± 28.05 | 0.95 |
Gender, n (%) | 0.49 | ||
male | 56 (83.60) | 21 (75.00) | |
female | 11 (16.40) | 7 (25.00) | |
Pathological grade, n (%) | 1.00 | ||
I + II | 55 (82.10) | 23 (82.10) | |
III | 12 (17.90) | 5 (17.90) | |
Vascular invasion, n (%) | 0.69 | ||
no | 62 (92.50) | 25 (89.30) | |
yes | 5 (7.50) | 3 (10.70) | |
T stage, n (%) | 0.68 | ||
T1 + T2 | 17 (27.00) | 5 (20.00) | |
T3 + T4 | 46 (73.00) | 20 (80.00) | |
TNM stage, n (%) | 0.49 | ||
I + II | 34 (53.10) | 11 (42.30) | |
III + IV | 30 (46.90) | 15 (57.70) |
Variables | Cut-Off Value | PH | Univariate/Time-Dependent Cox Regression | Multicollinearity | Multivariate Cox Regression | ||||
---|---|---|---|---|---|---|---|---|---|
p-Value | HR | 95%CI | p-Value | VIF | HR | 95%CI | p-Value | ||
Gender | 0.490 | 1.315 | |||||||
male | 1.000 | Reference | 1.000 | Reference | |||||
female | 0.271 | 0.084–0.877 | 0.029 ** | 0.214 | 0.058–0.794 | 0.021 ** | |||
Age (years) | 72 | 0.880 | |||||||
≤72 | 1.000 | Reference | |||||||
>72 | 0.676 | 0.333–1.373 | 0.279 | ||||||
Tumor length (cm) | 3 | 0.019 ** | |||||||
≤3 | 1.000 | Reference | |||||||
>3 | 1.078 | 0.752–1.546 | 0.680 | ||||||
Tumor volume (cm3) | 12 | 0.180 | |||||||
≤12 | 1.000 | Reference | |||||||
>12 | 0.605 | 0.329–1.112 | 0.106 | ||||||
Proportion of positive lymph nodes | 10% | 0.390 | 3.025 | ||||||
≤10% | 1.000 | Reference | 1.000 | Reference | |||||
>10% | 2.599 | 1.407–4.803 | 0.002 ** | 1.027 | 0.307–3.440 | 0.966 | |||
Pathological grade | 0.100 | 1.142 | |||||||
I + II | 1.000 | Reference | 1.000 | Reference | |||||
III | 2.215 | 1.100–4.460 | 0.026 ** | 1.778 | 0.796–3.970 | 0.160 | |||
Vascular invasion | 0.890 | ||||||||
no | 1.000 | Reference | |||||||
yes | 1.720 | 0.613–4.832 | 0.303 | ||||||
T stage | 0.820 | 1.336 | |||||||
T1 + T2 | 1.000 | Reference | 1.000 | Reference | |||||
T3 + T4 | 2.554 | 1.126–5.793 | 0.025 ** | 1.358 | 0.558–3.302 | 0.500 | |||
TNM stage | 0.260 | 2.778 | |||||||
I + II | 1.000 | Reference | 1.000 | Reference | |||||
III + IV | 2.049 | 1.110–3.784 | 0.022 ** | 2.812 | 0.799–9.890 | 0.107 | |||
CD39+ count | 2821 | 0.100 | |||||||
≤2821 | 1.000 | Reference | |||||||
>2821 | 1.616 | 0.879–2.969 | 0.122 | ||||||
CD39-expressing CD8+ T cells | 30.10% | 0.610 | |||||||
≤30.10% | 1.000 | Reference | |||||||
>30.10% | 1.722 | 0.726–4.084 | 0.217 | ||||||
CD39+ in CK+ region | 456 | 0.980 | 1.321 | ||||||
≤456 | 1.000 | Reference | 1.000 | Reference | |||||
>456 | 1.924 | 1.000–3.700 | 0.050 * | 1.347 | 0.603–3.012 | 0.468 | |||
CD39+ in CK− region | 3248 | 0.880 | |||||||
≤3248 | 1.000 | Reference | |||||||
>3248 | 1.424 | 0.771–2.633 | 0.259 | ||||||
CD39-expressing CD8+ T cells in CK+ region | 77.48% | 0.220 | 1.053 | ||||||
≤77.48% | 1.000 | Reference | 1.000 | Reference | |||||
>77.48% | 2.282 | 1.004–5.190 | 0.049 ** | 2.587 | 1.077–6.213 | 0.033 ** | |||
CD39-expressing CD8+ T cells in CK− region | 59.46% | 0.450 | 1.167 | ||||||
≤59.46% | 1.000 | Reference | 1.000 | Reference | |||||
>59.46% | 1.738 | 0.953–3.170 | 0.071 * | 3.090 | 1.352–7.064 | 0.008 ** |
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Liu, M.; Zhao, Y.; Xiao, Z.; Zhou, R.; Chen, X.; Cui, S.; Cao, S.; Huang, X.; Chen, T.; Huo, X.; et al. CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma. Cancers 2023, 15, 1184. https://doi.org/10.3390/cancers15041184
Liu M, Zhao Y, Xiao Z, Zhou R, Chen X, Cui S, Cao S, Huang X, Chen T, Huo X, et al. CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma. Cancers. 2023; 15(4):1184. https://doi.org/10.3390/cancers15041184
Chicago/Turabian StyleLiu, Meitong, Yaning Zhao, Zhuoyun Xiao, Rongmiao Zhou, Xiaodong Chen, Saijin Cui, Shiru Cao, Xi Huang, Tianyu Chen, Xiangran Huo, and et al. 2023. "CD39-Expressing CD8+ T Cells as a New Molecular Marker for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma" Cancers 15, no. 4: 1184. https://doi.org/10.3390/cancers15041184