Inhibition of MACC1-Induced Metastasis in Esophageal and Gastric Adenocarcinomas
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Tissue Samples
2.3. Cell Lines and Medium
2.4. Cloning and Transduction
2.5. MACC1 Expression Analysis
2.6. Proliferation
2.7. Migration
2.8. In Vitro Drug Treatment
2.9. Cell-Line-Derived Xenograft Model
2.10. Statistics
3. Results
3.1. Patients
3.2. MACC1 Expression
3.3. In Vitro Analysis
3.4. In Vivo Analysis
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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Total | MACC1 Low | Macc1 High | Exluced | p | |||||
---|---|---|---|---|---|---|---|---|---|
n | (%) | n | (%) | n | (%) | n | (%) | ||
Gender | |||||||||
Female | 131 | (36.4) | 14 | (10.7) | 82 | (62.6) | 35 | (26.7) | 0.083 |
Male | 229 | (63.6) | 41 | (17.9) | 129 | (56.3) | 59 | (25.8) | |
Age Group | |||||||||
<65 years | 159 | (44.2) | 37 | (23.9) | 111 | (69.8) | 53 | (33.3) | 0.051 |
≥65 years | 201 | (55.8) | 18 | (9.0) | 100 | (49.8) | 41 | (20.4) | |
Localization | |||||||||
AEG | 60 | (83.3) | 5 | (8.3) | 41 | (68.3) | 14 | (23.3) | 0.161 |
Stomach | 300 | (16.7) | 50 | (16.7) | 170 | (56.7) | 80 | (26.7) | |
Tumor Stage | |||||||||
T1 | 47 | (13.1) | 15 | (31.9) | 22 | (46.8) | 10 | (21.3) | 0.001 |
T2 | 140 | (38.9) | 25 | (17.9) | 81 | (57.9) | 34 | (24.3) | |
T3 | 122 | (33.9) | 10 | (8.2) | 86 | (70.5) | 26 | (21.3) | |
T4 | 32 | (8.9) | 5 | (15.6) | 22 | (68.8) | 5 | (15.6) | |
Tx | 19 | (5.3) | 0 | (0.0) | 0 | (0.0) | 19 | (100.0) | |
Node Stage | |||||||||
N0 | 105 | (29.29 | 19 | (18.1) | 51 | (48.6) | 35 | (33.3) | 0.293 |
N1 | 108 | (30.0) | 18 | (16.7) | 65 | (60.2) | 25 | (23.1) | |
N2 | 71 | (19.7) | 10 | (14.1) | 45 | (63.4) | 16 | (22.5) | |
N3 | 75 | (20.8) | 8 | (10.7) | 50 | (66.7) | 17 | (22.7) | |
Nx | 1 | (0.3) | - | - | - | - | - | - | |
Distant Metastasis | |||||||||
M0 | 245 | (68.1) | 48 | (19.6) | 149 | (60.8) | 48 | (19.6) | 0.012 |
M1 | 115 | (31.9) | 7 | (6.1) | 62 | (53.9) | 46 | (40.0) | |
Lymphatic Vessel Invasion | |||||||||
L0 | 115 | (31.9) | 24 | (20.9) | 66 | (57.4) | 25 | (21.7) | 0.07 |
L1 | 206 | (57.2) | 26 | (12.6) | 131 | (63.6) | 49 | (23.8) | |
Unknown | 39 | (10.8) | - | - | - | - | - | - | |
Vein Invasion | |||||||||
V0 | 201 | (55.8) | 37 | (18.4) | 122 | (60.7) | 42 | (20.9) | 0.139 |
V1 | 114 | (31.7) | 13 | (11.4) | 73 | (64.0) | 28 | (24.6) | |
Unknown | 45 | (12.5) | - | - | - | - | - | - | |
Grading | |||||||||
G1 | 1 | (0.3) | 1 | (100.0) | 0 | (0.0) | 0 | (0.0) | 0.001 |
G2 | 90 | (25.0) | 23 | (25.6) | 48 | (53.3) | 19 | (21.1) | |
G3 | 266 | (73.9) | 29 | (10.9) | 71 | (26.7) | 166 | (62.4) | |
Unknown | 3 | (0.8) | - | - | - | - | - | - | |
Lauren Classification | |||||||||
Intestinal | 122 | (33.9) | 26 | (21.3) | 69 | (56.6) | 27 | (22.1) | 0.048 |
Diffuse | 190 | (52.8) | 19 | (10.0) | 114 | (60.0) | 57 | (30.0) | |
Mixed | 45 | (12.5) | 8 | (17.8) | 27 | (60.0) | 10 | (22.2) | |
Unknown | 3 | (0.8) | - | - | - | - | - | - | |
Missmatch Repair System | |||||||||
proficient | 278 | (77.2) | 49 | (17.6) | 183 | (65.8) | 46 | (16.5) | <0.0001 |
deficient | 39 | (10.8) | 5 | (12.8) | 35 | (89.7) | 9 | (23.1) | |
unkown | 43 | (11.9) | - | - | - | - | - | - |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Median Survival Months (95% CI) | p | Odds Ratio | Low | High | p | |
Tumor Stage | ||||||
T1 | 181.19 (164.7–197.7) | <0.0001 | 1.798 | 1.467 | 2.203 | <0.0001 |
T2 | 79.72 (67.2–92.2) | |||||
T3 | 32.76 (23.5–42.1) | |||||
T4 | 14.13 (9.3–19.0) | |||||
Node Stage | ||||||
N0 | 135.79 (121.3–150.3) | <0.0001 | 1.595 | 1.353 | 1.879 | <0.0001 |
N1 | 64.32 (51.6–77.0) | |||||
N2 | 24.06 (16.6–31.6) | |||||
N3 | 17.92 (10.8–25.0) | |||||
Nx | 13.00 (13.0–13.0) | |||||
Lymphatic Vessel Invasion | ||||||
L0 | 119.68 (103.3–136.0) | <0.0001 | 1.004 | 0.774 | 1.302 | 0.976 |
L1 | 43.27 (34.9–51.6) | |||||
Lx | 32.7 (15.9–49.1) | |||||
Vein Invasion | ||||||
V0 | 99.00 (86.2–111.8) | <0.0001 | 1.003 | 0.778 | 1.292 | 0.984 |
V1 | 34.56 (24.7–44.4) | |||||
Vx | 32.22 (16.6–47.8) | |||||
Grading | ||||||
1 | - | 0.038 | 0.828 | 0.551 | 1.243 | 0.791 |
2 | 88.71 (72.7–104.7) | |||||
3 | 76.4 (65.8–87.0) | |||||
Lauren Classification | ||||||
intestinal | 95.97 (82.0–109.9) | 0.002 | 1.038 | 0.786 | 1.373 | 0.791 |
diffuse | 69.83 (56.8–82.9) | |||||
mixed | 69.40 (51.4–87.4) | |||||
Mismatch Repair System | ||||||
proficient | 47.22 (28.1–66.3) | 0.025 | 0.759 | 0.494 | 1.165 | 0.207 |
deficient | 79.77 (70.2–89.4) | |||||
MACC1 | ||||||
low | 87.06 (66.5–107.6) | 0.002 | 1.513 | 1.013 | 2.258 | 0.043 |
high | 54.20 (45.0–63.4) |
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Treese, C.; Werchan, J.; von Winterfeld, M.; Berg, E.; Hummel, M.; Timm, L.; Rau, B.; Daberkow, O.; Walther, W.; Daum, S.; et al. Inhibition of MACC1-Induced Metastasis in Esophageal and Gastric Adenocarcinomas. Cancers 2022, 14, 1773. https://doi.org/10.3390/cancers14071773
Treese C, Werchan J, von Winterfeld M, Berg E, Hummel M, Timm L, Rau B, Daberkow O, Walther W, Daum S, et al. Inhibition of MACC1-Induced Metastasis in Esophageal and Gastric Adenocarcinomas. Cancers. 2022; 14(7):1773. https://doi.org/10.3390/cancers14071773
Chicago/Turabian StyleTreese, Christoph, Jessica Werchan, Moritz von Winterfeld, Erika Berg, Michael Hummel, Lena Timm, Beate Rau, Ole Daberkow, Wolfgang Walther, Severin Daum, and et al. 2022. "Inhibition of MACC1-Induced Metastasis in Esophageal and Gastric Adenocarcinomas" Cancers 14, no. 7: 1773. https://doi.org/10.3390/cancers14071773