Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components
Abstract
1. Introduction
2. Results
3. Discussion
4. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AKT | protein kinase B |
BMI | body mass index |
CT | computed tomography |
CTLA4 | cytotoxic T-lymphocyte-associated protein 4 |
DSP | digital spatial profiler |
ER | estrogen receptor |
FDR | false discovery rate |
GZMB | Granzyme B |
HER2 | human epidermal growth factor receptor 2 |
ICI | immune checkpoint inhibitor |
INPP4B | inositol polyphosphate-4-phosphatase type II B |
L3 | the third lumbar vertebra |
MTOR | mechanistic target of rapamycin kinase |
panCK | pan-cytokeratin |
PD-1 | programmed cell death protein 1 |
PD-L1 | programmed death ligand 1 |
PI3K | phosphoinositide 3-kinase |
PLCG1 | phospholipase C gamma 1 |
PR | progesterone receptor |
PRAS40 | proline-rich Akt substrate of 40 kDa |
PTEN | phosphatase and tensin homolog |
ROI | region of interest |
SD | standard deviation |
SMI | skeletal muscle index |
TAT | total adipose tissue |
TCGA | The Cancer Genome Atlas |
TIL | tumor-infiltrating lymphocyte |
TSC2 | tuberous sclerosis complex 2 |
TSM | total skeletal muscle |
WC | waist circumference |
References
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Characteristic | Mean (SD) or No. % |
---|---|
Age at diagnosis (years) | 56.8 (10.5) |
Age at CT scan (years) | 57.2 (10.3) |
Waist circumference (cm) | 99.4 (13.9) |
Race | |
White | 43 (82.7) |
Black | 9 (17.3) |
Cancer stage | |
I | 17 (32.7) |
II | 26 (50.0) |
III | 9 (17.3) |
Tumor grade | |
I | 5 (9.7) |
II | 28 (53.8) |
III | 19 (36.5) |
Tumor size | |
<25 mm | 24 (46.2) |
≥25 mm | 17 (32.7) |
Missing | 11 (21.1) |
ER status | |
Positive | 46 (88.5) |
Negative | 6 (11.5) |
PR status | |
Positive | 43 (82.7) |
Negative | 9 (17.3) |
HER2 status | |
Positive | 10 (19.3) |
Negative | 41 (78.8) |
Missing | 1 (1.9) |
Molecular subtype a | |
HR+/HER2+ | 9 (17.3) |
HR+/HER2- | 37 (71.2) |
HR-/HER2+ | 1 (1.9) |
HR-/HER2-(triple-negative) | 4 (7.7) |
Missing | 1 (1.9) |
Chemotherapy | |
Yes | 24 (46.2) |
No | 27 (51.9) |
Missing | 1 (1.9) |
Body composition | |
Adequate | 22 (42.3) |
High adiposity | 13 (25.0) |
Low muscle | 14 (26.9) |
High adiposity with low muscle | 3 (5.8) |
Marker | Tumor a, Median (IQR) | Stroma a, Median (IQR) | p-Value | FDR-Corrected p-Value |
---|---|---|---|---|
PanCk | 9.13 (2.6) | 5.33 (2.06) | 3.47 × 10−38 | 1.49 × 10−36 |
ER-alpha | 5.76 (3.58) | 2.66 (3.14) | 1.88 × 10−28 | 4.04 × 10−27 |
Phospho-GSK3B (S9) | 2.41 (3.32) | 0 (1.21) | 5.31 × 10−22 | 7.61 × 10−21 |
EpCAM | 3.71 (3.13) | 1.28 (2.1) | 1.77 × 10−21 | 1.90 × 10−20 |
Fibronectin | 6.89 (3.31) | 9.39 (3.04) | 1.34 × 10−20 | 1.15 × 10−19 |
Her2 | 3.48 (2.33) | 1.87 (2.12) | 4.60 × 10−19 | 3.30 × 10−18 |
INPP4B | 5.06 (2.87) | 3.16 (2) | 9.51 × 10−19 | 5.84 × 10−18 |
PR | 3.69 (4.17) | 1.63 (2.05) | 1.51 × 10−18 | 8.12 × 10−18 |
MET | 2.59 (3.05) | 1.31 (2.2) | 2.64 × 10−16 | 1.26 × 10−15 |
Bcl-2 | 4.58 (2.51) | 3.37 (1.87) | 3.30 × 10−13 | 1.42 × 10−12 |
SMA | 8.5 (2.38) | 10.16 (2.03) | 5.92 × 10−11 | 2.31 × 10−10 |
NY-ESO-1 | 1.83 (3.24) | 0.79 (2.32) | 1.92 × 10−10 | 6.88 × 10−10 |
Phospho-GSK3A (S21)/Phospho-GSK3B (S9) | 2.76 (2.8) | 1.26 (1.67) | 3.06 × 10−10 | 1.01 × 10−9 |
Ki-67 | 2.7 (2.62) | 2.25 (1.98) | 4.18 × 10−8 | 1.28 × 10−7 |
FOXP3 | 0.26 (2.24) | 0 (0.85) | 1.06 × 10−7 | 3.04 × 10−7 |
Pan-AKT | 5.92 (2.42) | 4.95 (1.78) | 1.80 × 10−7 | 4.84 × 10−7 |
CD45 | 3.53 (2.7) | 4.46 (2.36) | 2.08 × 10−7 | 5.26 × 10−7 |
PLCG1 | 1.52 (2.71) | 1.06 (2.06) | 4.92 × 10−7 | 1.18 × 10−6 |
CD163 | −0.02 (2.31) | 0.23 (1.72) | 1.12 × 10−6 | 2.41 × 10−6 |
MART1 | 0.9 (3.34) | 0.1 (2.09) | 1.11 × 10−6 | 2.41 × 10−6 |
HLA-DR | 3.41 (3.13) | 4.58 (2.79) | 2.46 × 10−6 | 5.04 × 10−6 |
Phospho-PRAS40 (T246) | 1.71 (3.18) | 0.7 (2.23) | 8.68 × 10−6 | 1.70 × 10−5 |
CD34 | 2.62 (2.99) | 3.67 (2.74) | 9.66 × 10−6 | 1.81 × 10−5 |
CD11c | 2.91 (2.96) | 3.69 (2.16) | 6.63 × 10−5 | 0.000118788 |
CD3 | 1.32 (3.61) | 2.26 (2.97) | 7.21 × 10−5 | 0.000124012 |
FAP-alpha | 0.16 (2.74) | 1.06 (2.45) | 0.000546 | 0.000903 |
Phospho-AKT1 (S473) | 2.1 (2.96) | 1.46 (2.02) | 0.00173 | 0.002755185 |
CD66b | −0.08 (1.84) | 0 (0.89) | 0.00405 | 0.006219643 |
GZMB | 3.39 (2.81) | 3.59 (2.39) | 0.0102 | 0.015124138 |
PD-1 | 1 (2.81) | 0.95 (2.1) | 0.0125 | 0.017916667 |
CD45RO | 1.71 (2.38) | 1.27 (2.41) | 0.0139 | 0.019280645 |
CD20 | 0.85 (2.47) | 0.79 (1.84) | 0.0172 | 0.0231125 |
CD4 | 2.09 (2.95) | 2.63 (2.83) | 0.0252 | 0.032836364 |
Beta-2-microglobulin | 2.52 (2.76) | 2.3 (2.3) | 0.0322 | 0.040723529 |
CTLA4 | −0.02 (4.8) | 0 (2.9) | 0.0353 | 0.043368571 |
PD-L1 | −0.11 (1.69) | −0.03 (1.05) | 0.0418 | 0.049927778 |
CD14 | 2.63 (3.38) | 2.95 (2.24) | 0.0496 | 0.057643243 |
CD56 | 2.01 (2.95) | 2.03 (2.14) | 0.0638 | 0.07009 |
Phospho-Tuberin (T1462) | 0 (2.15) | −0.04 (0.95) | 0.0637 | 0.07009 |
PTEN | 1.31 (3.36) | 1.21 (2.53) | 0.0652 | 0.07009 |
CD68 | 3.27 (2.82) | 3.6 (1.64) | 0.445 | 0.466707317 |
CD8 | 3.08 (3.15) | 3.38 (2.81) | 0.599 | 0.613261905 |
S100B | 2.5 (3.65) | 2.73 (4.1) | 0.701 | 0.701 |
Basic Model a | Full Model b | |||||||
---|---|---|---|---|---|---|---|---|
Body Composition Type (Compared with Adequate Type) | Marker | Tissue Compartment | Log2-Fold Changes (95% CI) | p Value | FDR-Corrected p Value | Log2-Fold Changes (95% CI) | p Value | FDR Corrected p |
Low muscle | Pan-AKT | Tumor | −0.76 (−1.63, 0.12) | 0.1077 | 0.9756 | −0.92 (−1.71, −0.13) | 0.0427 | 0.8243 |
Low muscle | CTLA4 | Tumor | 0.60 (0.07, 1.28) | 0.0362 | 0.9756 | 0.53 (0.04, 1.03) | 0.0589 | 0.8244 |
Low muscle | INPP4B | Stroma | 1.14 (0.59, 1.69) | 0.0003 | 0.0270 | 1.18 (0.65, 1.72) | 0.0003 | 0.0280 |
High adiposity | INPP4B | Stroma | 0.87 (0.31, 1.43) | 0.0054 | 0.2200 | 0.64 (0.06, 1.23) | 0.0578 | 0.4168 |
High adiposity | CD8 | Stroma | 1.35 (0.38, 2.32) | 0.0115 | 0.2200 | 1.16 (0.17, 2.15) | 0.0429 | 0.4168 |
High adiposity | CD45RO | Stroma | 1.10 (0.29, 1.91) | 0.0131 | 0.2200 | 0.95 (0.14, 1.76) | 0.0425 | 0.4168 |
High adiposity | GZMB | Stroma | 1.02 (0.24, 1.80) | 0.0170 | 0.2382 | 0.63 (−0.17, 1.43) | 0.1656 | 0.6223 |
High adiposity | CD20 | Stroma | 0.52 (0.03, 1.02) | 0.0434 | 0.3397 | 0.61 (0.09, 1.13) | 0.0314 | 0.4168 |
High adiposity | CD3 | Stroma | 1.14 (0.10, 2.18) | 0.0440 | 0.3397 | 1.07 (−0.02, 2.16) | 0.0884 | 0.4950 |
High adiposity/low muscle | Phospho-tuberin (T1462) | Tumor | −1.08 (−2.28, 0.12) | 0.0946 | 0.9900 | −1.52 (−2.67, −0.39) | 0.0205 | 0.4735 |
High adiposity/low muscle | Phospho-PRAS40 (T246) | Tumor | −1.41 (−3.11, 0.28) | 0.1197 | 0.9900 | −1.96 (−3.59, −0.36) | 0.0338 | 0.4735 |
High adiposity/low muscle | Phospho-PRAS40 (T246) | Stroma | −1.36 (−2.60, −0.11) | 0.0445 | 0.3397 | −1.39 (−2.62, −0.16) | 0.0512 | 0.4168 |
High adiposity/low muscle | CTLA4 | Stroma | 0.98 (0.09, 1.88) | 0.0436 | 0.3397 | 1.10 (0.19, 2.02) | 0.0383 | 0.4168 |
High adiposity/low muscle | PD-1 | Stroma | −0.98 (−2.05, 0.08) | 0.0873 | 0.4398 | −1.22 (−2.29, −0.16) | 0.0480 | 0.4168 |
High adiposity/low muscle | CD14 | Stroma | −2.43 (−4.13, −0.73) | 0.0096 | 0.2200 | −2.18 (−3.82, −0.54) | 0.0231 | 0.4168 |
High adiposity/low muscle | PLCG1 | Stroma | −1.28 (−2.37, −0.19) | 0.0315 | 0.3397 | −1.31 (−2.36, −0.26) | 0.0264 | 0.4168 |
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Cheng, T.-Y.D.; Fu, D.A.; Falzarano, S.M.; Zhang, R.; Datta, S.; Zhang, W.; Omilian, A.R.; Aduse-Poku, L.; Bian, J.; Irianto, J.; et al. Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components. Int. J. Mol. Sci. 2024, 25, 13428. https://doi.org/10.3390/ijms252413428
Cheng T-YD, Fu DA, Falzarano SM, Zhang R, Datta S, Zhang W, Omilian AR, Aduse-Poku L, Bian J, Irianto J, et al. Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components. International Journal of Molecular Sciences. 2024; 25(24):13428. https://doi.org/10.3390/ijms252413428
Chicago/Turabian StyleCheng, Ting-Yuan David, Dongtao Ann Fu, Sara M. Falzarano, Runzhi Zhang, Susmita Datta, Weizhou Zhang, Angela R. Omilian, Livingstone Aduse-Poku, Jiang Bian, Jerome Irianto, and et al. 2024. "Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components" International Journal of Molecular Sciences 25, no. 24: 13428. https://doi.org/10.3390/ijms252413428
APA StyleCheng, T.-Y. D., Fu, D. A., Falzarano, S. M., Zhang, R., Datta, S., Zhang, W., Omilian, A. R., Aduse-Poku, L., Bian, J., Irianto, J., Asirvatham, J. R., & Campbell-Thompson, M. (2024). Association of Computed Tomography Scan-Assessed Body Composition with Immune and PI3K/AKT Pathway Proteins in Distinct Breast Cancer Tumor Components. International Journal of Molecular Sciences, 25(24), 13428. https://doi.org/10.3390/ijms252413428