Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma—An Unexpected Correlation to Guide Future Treatment?
Abstract
:1. Introduction
2. Results
2.1. Clinicopathological Patient Characteristics
2.2. Association of M3 Low and High Expression with Clinicopathological Features in CRC
2.3. Immune Cell Density According to M3 Low and High Expression
2.4. Survival Analysis
2.5. Uni- and Multivariate Cox Regression Survival Analysis of Low and High Expression of M3R
3. Discussion
3.1. Key Findings
3.2. Correlation with Previous Literature
3.3. Implications
3.4. Future Perspective and Possibilites
4. Materials and Methods
4.1. Tissue Microarray (TMA) Construction
4.2. Clinicopathological Features
4.3. Immunohistochemistry
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient Characteristic | N or Mean | Percentage or Range | |
---|---|---|---|
Age, years (median, mean) | 70, 68.8 | 30–96 | |
Tumor size in mm (median, mean) | 50, 50.8 | 5–170 | |
Sex | Female | 407 | 50% |
Male | 347 | 43% | |
Anatomic site of the tumor | Left-sided | 520 | 64% |
Right-sided | 232 | 29% | |
Stage IA, T1N0 | 26 | 3% | |
UICC stage | Stage IB, T2N0 | 71 | 9% |
Stage IIA, T3N0 | 254 | 31% | |
Stage IIB-C, T4N0 | 34 | 4% | |
Stage III, >N0 | 342 | 42% | |
Tumor border configuration | Infiltrative | 516 | 63% |
Pushing | 221 | 27% | |
Vascular invasion | No | 532 | 65% |
Yes | 207 | 25% | |
Microsatellite stability | Proficient | 658 | 81% |
Deficient | 96 | 96% | |
Rectal cancers | 288 | 35% | |
Rectosigmoid cancers | 50 | 6% | |
Overall survival time (months) | 58.9 | 1–152 | |
5-year survival % (95% CI) | 0.45 | 0.42–0.49 |
Parameter | M3R-Low | M3R-High | p-Value | |||
---|---|---|---|---|---|---|
N = 67 (10.6%) | N = 568 (89.5%) | |||||
Age | Years, mean ± SD | 67.3 ± 11.9 | 68.8 ± 11.4 | 0.418 | ||
Tumor diameter | mm, mean ± SD | 50.5 ± 22.1 | 50.9 ± 20.1 | 0.760 | ||
Gender | Female | 33 (49.3%) | 294 (51.7%) | 0.640 | ||
Male | 31 (46.3%) | 244 (42.9%) | ||||
Tumor location | Left-sided | 42 (62.7%) | 379 (66.7%) | 0.401 | ||
Right-sided | 22 (32.8%) | 157 (27.6%) | ||||
Histologic subtype | Mucinous | 6 (9.0%) | 22 (3.9%) | <0.001 | ||
Non-mucinous | 61 (91.0%) | 546 (96.1%) | ||||
pT stage | pT1–2 | 14 (20.9%) | 105 (18.5%) | 0.436 | ||
pT3–4 | 44 (65.7%) | 425 (74.8%) | ||||
pN stage | pN0 | 32 (47.8%) | 279 (49.1%) | 0.690 | ||
pN1–2 | 31 (46.3%) | 243 (42.8%) | ||||
Tumor grade | G1 | 3 (4.5 %) | 14 (2.5%) | 0.002 | ||
G2 | 45 (67.1%) | 487 (85.7%) | ||||
G3 | 10 (14.9%) | 29 (5.1%) | ||||
Vascular invasion | Absent | 39 (58.2%) | 387 (68.1%) | 0.350 | ||
Present | 19 (28.4%) | 143 (25.2%) | ||||
Tumor border | Pushing | 12 (17.9%) | 171 (30.1%) | 0.068 | ||
Infiltrating | 46 (68.7%) | 357 (62.9%) | ||||
PTL inflammation | Absent | 47 (70.2%) | 406 (71.5%) | 0.446 | ||
Present | 11 (16.4%) | 124 (21.8%) | ||||
Microsatellite stability | Deficient | 8 (11.9%) | 60 (10.6%) | 0.747 | ||
Proficient | 56 (83.6%) | 478 (84.2%) | ||||
5-year survival rate | (95% CI) | 42% (0.30–0.54) | 46% (0.41–0.50) | 0.073 |
M3-Low | M3-High | p-Value | |
---|---|---|---|
Mean ± SD | Mean ± SD | ||
CD8 | 18.9 ± 32.6 | 8.67 ± 16.8 | 0.018 |
FOXP3 | 30.3 ± 34.9 | 34.0 ± 39.4 | 0.638 |
IL17 | 10.3 ± 15.6 | 15.8 ± 29.1 | 0.141 |
TIA-1 | 4.5 ± 8.0 | 2.7 ± 6.9 | 0.047 |
CD16 | 30.0 ± 32.1 | 32.9 ± 32.1 | 0.292 |
OX40 | 37.3 ± 49.0 | 45.5 ± 60.5 | 0.380 |
Variable | Univariate Regression | Multivariate Regression | ||
---|---|---|---|---|
OR (95% CI) | p-Value | OR (95% CI) | p-Value | |
Sex | ||||
Female | Reference | Reference | ||
Male | 1.28 (1.05–1.56) | 0.015 | 1.35 (1.05–1.74) | 0.017 |
Age | ||||
<60 | Reference | Reference | ||
>60 | 1.03 (1.02–1.04) | <0.001 | 1.04 (1.03–1.05) | <0.001 |
Vascular invasion | ||||
Absent | Reference | Reference | ||
Present | 2.57; 2.09–3.16; | <0.001 | 2.03 (1.55–2.66) | <0.001 |
Invasive tumor margin configuration | ||||
Pushing | Reference | Reference | ||
Infiltrative | 2.02 (1.58–2.59) | <0.001 | 1.34 (0.96–1.84) | 0.07 |
Microsatellite stability | ||||
Deficient | Reference | Reference | ||
Proficient | 1.61 (1.15–2.56) | 0.005 | 1.59 (1.01–2.49) | 0.043 |
pT Stage | ||||
pT 1–2 | Reference | Reference | ||
pT 3–4 | 3.09 (2.19–4.35) | <0.001 | 2.30 (1.47–3.60) | <0.001 |
pN Stage | ||||
pN 0 | Reference | Reference | ||
pN > 0 | 2.82 (2.28–3.47) | <0.001 | 2.26 (1.72–2.96) | <0.001 |
Grade | ||||
G0-G1 | Reference | Reference | ||
G2-G3 | 6.06. (1.94–18.87) | 0.002 | 2.58 (0.62–10.80) | 0.193 |
M3R expression | ||||
low | Reference | Reference | ||
high | 0.73 (0.52–1.03) | 0.075 | 0.52 (0.35–0.78) | 0.001 |
CD8 expression | ||||
low | Reference | Reference | ||
high | 0.99 (0.98–1.0) 2 | 0.014 | 1.00 (0.99–1.01) 2 | 0.609 |
TIA-1 expression | ||||
Low | Reference | Reference | ||
High | 0.99 (0.98–1.0) 2 | 0.24 | 0.97 (0.94–0.99) 2 | 0.014 |
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Lobbes, L.A.; Schütze, M.A.; Droeser, R.; Arndt, M.; Pozios, I.; Lauscher, J.C.; Hering, N.A.; Weixler, B. Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma—An Unexpected Correlation to Guide Future Treatment? Int. J. Mol. Sci. 2023, 24, 8198. https://doi.org/10.3390/ijms24098198
Lobbes LA, Schütze MA, Droeser R, Arndt M, Pozios I, Lauscher JC, Hering NA, Weixler B. Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma—An Unexpected Correlation to Guide Future Treatment? International Journal of Molecular Sciences. 2023; 24(9):8198. https://doi.org/10.3390/ijms24098198
Chicago/Turabian StyleLobbes, Leonard A., Marcel A. Schütze, Raoul Droeser, Marco Arndt, Ioannis Pozios, Johannes C. Lauscher, Nina A. Hering, and Benjamin Weixler. 2023. "Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma—An Unexpected Correlation to Guide Future Treatment?" International Journal of Molecular Sciences 24, no. 9: 8198. https://doi.org/10.3390/ijms24098198