The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Specimens
2.2. IHC
2.3. Data Analyses of TCGA and GEO Database
2.4. Statistical Analysis
3. Results
3.1. The Expression Patterns of Tumor Cell-Intrinsic cGAS-STING in pMMR/MSS CRC
3.2. Down-Regulation of the Expression of cGAS-STING in Tumor Cells in the Advanced Stages of pMMR CRC
3.3. Associations between the Tumor Cell-Intrinsic Expression of cGAS-STING and the Infiltration of CD8+ and CD4+ T Cells in pMMR/MSS CRC
3.4. Associations between the Tumor Cell-Intrinsic Expression of cGAS-STING and Clinical Outcomes in Patients with pMMR/MSS CRC
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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pMMR CRC All | cGAS+/STING+ | cGAS+/STING− | cGAS−/STING+ | cGAS−/STING− | |||
---|---|---|---|---|---|---|---|
(n = 243) | (n = 24) | (n = 34) | (n = 47) | (n = 138) | p-Value | ||
Age | <70 | 121 | 11 | 20 | 17 | 73 | 0.1523 |
70≤ | 122 | 13 | 14 | 30 | 65 | ||
Gender | Male | 154 | 18 | 25 | 30 | 81 | 0.2393 |
Female | 89 | 6 | 9 | 17 | 57 | ||
Tumor location | Proximal | 78 | 12 | 16 | 16 | 34 | 0.0379 |
Distal | 68 | 4 | 10 | 15 | 39 | ||
Rectum | 97 | 8 | 8 | 16 | 65 | ||
Tumor differentiation | Well/Moderate | 234 | 22 | 31 | 47 | 134 | 0.1116 |
Poor | 9 | 2 | 3 | 0 | 4 | ||
T stage | Tis | 13 | 3 | 0 | 6 | 4 | 0.0113 |
T1 | 31 | 3 | 4 | 6 | 18 | ||
T2 | 35 | 1 | 5 | 14 | 15 | ||
T3 | 101 | 10 | 16 | 13 | 62 | ||
T4 | 63 | 7 | 9 | 8 | 39 | ||
N stage | N0 | 144 | 13 | 17 | 31 | 83 | 0.4967 |
N1-3 | 99 | 11 | 17 | 16 | 55 | ||
M stage | M0 | 213 | 20 | 30 | 44 | 119 | 0.5267 |
M1 | 30 | 4 | 4 | 3 | 19 | ||
TNM stage | 0 | 13 | 3 | 0 | 6 | 4 | 0.0658 |
I | 52 | 4 | 7 | 15 | 26 | ||
II | 72 | 6 | 9 | 9 | 48 | ||
III | 76 | 7 | 14 | 14 | 41 | ||
IV | 30 | 4 | 4 | 3 | 19 | ||
PD-L1 | Positive | 12 | 2 | 3 | 2 | 5 | 0.5246 |
Negative | 231 | 22 | 31 | 45 | 133 | ||
Recurrence | Yes | 40 | 2 | 5 | 8 | 25 | 0.6752 |
No | 180 | 19 | 26 | 37 | 98 | ||
Not available | 23 | 3 | 3 | 2 | 15 | - |
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Nakajima, S.; Kaneta, A.; Okayama, H.; Saito, K.; Kikuchi, T.; Endo, E.; Matsumoto, T.; Fukai, S.; Sakuma, M.; Sato, T.; et al. The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer. Cancers 2023, 15, 2826. https://doi.org/10.3390/cancers15102826
Nakajima S, Kaneta A, Okayama H, Saito K, Kikuchi T, Endo E, Matsumoto T, Fukai S, Sakuma M, Sato T, et al. The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer. Cancers. 2023; 15(10):2826. https://doi.org/10.3390/cancers15102826
Chicago/Turabian StyleNakajima, Shotaro, Akinao Kaneta, Hirokazu Okayama, Katsuharu Saito, Tomohiro Kikuchi, Eisei Endo, Takuro Matsumoto, Satoshi Fukai, Mei Sakuma, Takahiro Sato, and et al. 2023. "The Impact of Tumor Cell-Intrinsic Expression of Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) on the Infiltration of CD8+ T Cells and Clinical Outcomes in Mismatch Repair Proficient/Microsatellite Stable Colorectal Cancer" Cancers 15, no. 10: 2826. https://doi.org/10.3390/cancers15102826