Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Expression of ADAM17 in Pan-Cancer and HCC
2.2. Prognostic Role of ADAM17 and Its Correlation with HCC Clinicopathological Features
2.3. Investigating the Function of ADAM17 and Related Pathways
2.4. Association between ADAM17 Expression, Immune Infiltration, and Copy Number
2.5. Gene Profile Analysis of ADAM17
2.6. PPI Network Analysis
2.7. Verification of ADAM17 Expression and Its Prognostic Roles in HCC
2.8. In Vitro Roles of ADAM17 in HCC Cell Growth
2.9. In Vitro Roles of ADAM17 in HCC Metastasis
2.10. In Vivo Investigation of the Role of ADAM17 in HCC Growth
2.11. Verification of the Correlation between ADAM17 and Immune Cell Infiltration
3. Discussion
4. Materials and Methods
4.1. Datasets and Data Preprocessing
4.2. ADAM17 Association with Patient Survival and Clinicopathological Features
4.3. Enrichment Analysis
4.4. Immune Cell Infiltration Analysis
4.5. Mutation Analysis of ADAM17
4.6. PPI Network Analysis
4.7. Patients and Tumour Samples
4.8. Immunohistochemistry
4.9. Cell Culture and Stable Cell Construction
4.10. Western Blotting
4.11. Cell Proliferation and Colony Formation Assays
4.12. Wound Healing Assays
4.13. Transwell Matrigel Invasion and Migration Assay
4.14. In Vivo Growth Assays
4.15. Statistical Analyses
5. Conclusions and Future Directions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Overall $ | Characteristics | Overall |
---|---|---|---|
Pathologic T stage, n (%) | Gender, n (%) | ||
T1 | 183 (49.3%) | Female | 121 (32.4%) |
T2 | 95 (25.6%) | Male | 253 (67.6%) |
T3 | 80 (21.6%) | Age, n (%) | |
T4 | 13 (3.5%) | ≤60 | 177 (47.5%) |
Pathologic N stage, n (%) | >60 | 196 (52.5%) | |
N0 | 254 (98.4%) | BMI, n (%) | |
N1 | 4 (1.6%) | ≤25 | 177 (52.5%) |
Pathologic M stage, n (%) | >25 | 160 (47.5%) | |
M0 | 268 (98.5%) | Histologic grade, n (%) | |
M1 | 4 (1.5%) | G1 | 55 (14.9%) |
Pathologic stage, n (%) | G2 | 178 (48.2%) | |
Stage I | 173 (49.4%) | G3 | 124 (33.6%) |
Stage II | 87 (24.9%) | G4 | 12 (3.3%) |
Stage III | 85 (24.3%) | AFP (ng/mL), n (%) | |
Stage IV | 5 (1.4%) | ≤400 | 215 (76.8%) |
>400 | 65 (23.2%) |
Clinicopathological Parameters | Level | ADAM17 Expression | p-Value | |
---|---|---|---|---|
Low Expression | High Expression | |||
N | 25 | 54 | ||
Age (median [IQR]) | 51.00 [46.00, 59.00] | 56.00 [49.00, 59.75] | 0.509 | |
Sex (%) | female | 10 (40.0) | 12 (22.2) | 0.114 |
male | 15 (60.0) | 42 (77.8) | ||
Cirrhosis (%) | no | 2 (8.0) | 2 (3.7) | 0.587 |
yes | 23 (92.0) | 52 (96.3) | ||
Capsule (%) | incomplete | 2 (8.0) | 10 (18.5) | 0.458 |
intact | 6 (24.0) | 9 (16.7) | ||
unclear | 17 (68.0) | 35 (64.8) | ||
MVI risk (%) | M0 | 14 (56.0) | 24 (44.4) | 0.678 |
M1 | 9 (36.0) | 25 (46.3) | ||
M2 | 2 (8.0) | 5 (9.3) | ||
Differentiation (%) | low | 0 (0.0) | 8 (14.8) | 0.001 |
moderate | 19 (76.0) | 41 (75.9) | ||
high | 6 (24.0) | 1 (1.9) | ||
unclear | 0 (0.0) | 4 (7.4) | ||
Histologic Grade (%) | G1 | 6 (24.0) | 1 (1.9) | 0.001 |
G2 | 19 (76.0) | 41 (75.9) | ||
G3 | 0 (0.0) | 8 (14.8) | ||
Gx | 0 (0.0) | 4 (7.4) | ||
Stage (%) | I | 12 (48.0) | 10 (18.5) | 0.021 |
II | 10 (40.0) | 23 (42.6) | ||
III | 3 (12.0) | 18 (33.3) | ||
IV | 0 (0.0) | 3 (5.6) | ||
History of hepatitis (%) | no | 3 (12.0) | 3 (5.6) | 0.374 |
yes | 22 (88.0) | 51 (94.4) | ||
TBIL μmol/L (median [IQR]) | 13.90 [11.80, 21.50] | 16.00 [11.60, 24.60] | 0.602 | |
ALB g/L (median [IQR]) | 37.70 [34.70, 38.50] | 37.80 [36.20, 41.38] | 0.158 | |
PT s (median [IQR]) | 12.10 [11.20, 12.60] | 12.70 [12.00, 13.35] | 0.038 | |
Child Pugh (%) | A | 24 (96.0) | 50 (92.6) | 1 |
B | 1 (4.0) | 3 (5.6) | ||
C | 0 (0.0) | 1 (1.9) | ||
Tumor size (%) | MHCC | 4 (16.0) | 14 (25.9) | 0.702 |
SHCC | 10 (40.0) | 22 (40.7) | ||
LHCC | 9 (36.0) | 14 (25.9) | ||
HHCC | 2 (8.0) | 4 (7.4) | ||
Serum AFP ng/mL (%) | ≤400 | 19 (76.0) | 44 (81.5) | 0.563 |
>400 | 6 (24.0) | 10 (18.5) |
Clinicopathological Parameters | Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|---|
HR | 95% CI | p-Value | HR | 95% CI | p-Value | ||
Age | 1.01 | 0.98–1.04 | 0.449 | NA | NA | NA | |
ALB g/L | 1 | 0.92–1.07 | 0.918 | NA | NA | NA | |
Capsule | Incomplete | Reference | |||||
intact | 0.83 | 0.34–2.04 | 0.679 | NA | NA | NA | |
unclear | 0.86 | 0.42–1.75 | 0.678 | NA | NA | NA | |
Child Pugh | 3.41 | 1.45–8.02 | 0.005 | 3.48 | 1.09–11.11 | 0.0356 | |
Cirrhosis | No | Reference | |||||
yes | 5.56 | 0.77–40.24 | 0.09 | NA | NA | NA | |
Differentiation | Low | Reference | |||||
high | 0.24 | 0.05–1.03 | 0.054 | NA | NA | NA | |
moderate | 0.74 | 0.29–1.92 | 0.535 | NA | NA | NA | |
unclear | 1.73 | 0.46–6.47 | 0.416 | NA | NA | NA | |
group | Low expression | Reference | |||||
High expression | 4.07 | 2.06–8.08 | 0 | 3 | 1.4–6.42 | 0.0047 | |
Histologic Grade | G1 | Reference | |||||
G2 | 3.13 | 0.97–10.13 | 0.057 | 1.83 | 0.53–6.37 | 0.341 | |
G3 | 4.22 | 0.98–18.3 | 0.054 | 1.35 | 0.27–6.88 | 0.7159 | |
Gx | 7.3 | 1.59–33.56 | 0.011 | 3.44 | 0.67–17.77 | 0.1405 | |
History of hepatitis | No | Reference | |||||
yes | 1.39 | 0.55–3.49 | 0.487 | NA | NA | NA | |
MVI risk | 1.11 | 0.72–1.7 | 0.633 | NA | NA | NA | |
PT s | 1.31 | 1.1–1.56 | 0.002 | 1.07 | 0.84–1.35 | 0.601 | |
Serum AFP ng/mL | ≤400 | Reference | |||||
>400 | 1.37 | 0.72–2.6 | 0.332 | NA | NA | NA | |
Sex | Female | Reference | |||||
male | 1.29 | 0.71–2.33 | 0.403 | NA | NA | NA | |
Stage | 1.45 | 1.04–2.03 | 0.029 | 1.42 | 0.98–2.05 | 0.063 | |
TBIL μmol/L | 1.02 | 0.99–1.05 | 0.162 | NA | NA | NA | |
Tumor size | 1.09 | 0.81–1.46 | 0.57 | NA | NA | NA |
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Ding, T.; Yu, Y.; Gao, L.; Xiang, L.; Xu, B.; Gu, B.; Chen, H. Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma. Int. J. Mol. Sci. 2023, 24, 17069. https://doi.org/10.3390/ijms242317069
Ding T, Yu Y, Gao L, Xiang L, Xu B, Gu B, Chen H. Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2023; 24(23):17069. https://doi.org/10.3390/ijms242317069
Chicago/Turabian StyleDing, Tianlong, Yang Yu, Lei Gao, Lin Xiang, Bo Xu, Baohong Gu, and Hao Chen. 2023. "Predictive Roles of ADAM17 in Patient Survival and Immune Cell Infiltration in Hepatocellular Carcinoma" International Journal of Molecular Sciences 24, no. 23: 17069. https://doi.org/10.3390/ijms242317069