Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes—Obesity as a Crucial Player
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population and Ethical Approval
2.2. Sample Characteristics
2.3. Hematoxylin–Eosin Staining
2.4. Immunohistochemistry Assays
2.5. Statistical Analysis
3. Results
3.1. Demographic and Clinicopathological Data
3.2. Expression of Glycolysis and Gluconeogenesis Rate-Limiting Enzymes
3.3. Correlation between Rate-Limiting Enzymes Expression and Clinicopathological Features
3.4. Intratumor Adipose Tissue Deposition
3.5. Inflammatory Infiltration
3.6. Correlation between Tumor Cell Enzymatic Expression and Obesity-Associated Conditions
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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n (%) | Total | p-Value BMI Analysis | p-Value MS Analysis | p-Value mBMI Analysis |
---|---|---|---|---|
62 (100.0%) | ||||
Age at diagnosis | ||||
(Mean ± SD) | 57.48 ± 10.53 | 0.480 | 0.218 | 0.604 |
BMI categories | ||||
Normal weight | 32 (51.6%) | - | 0.974 | - |
Obese | 30 (48.4%) | |||
Molecular subtypes | ||||
Luminal A | 16 (25.8%) | 0.974 | - | - |
Luminal B | 16 (25.8%) | |||
Triple negative | 16 (25.8%) | |||
HER2+ | 14 (22.6%) | |||
Topographic localization | ||||
CQ | 3 (4.8%) | 0.680 | 0.052 | 0.075 |
IOQ | 4 (6.5%) | |||
SOQ | 21 (33.9%) | |||
SIQ | 4 (6.5%) | |||
Multiple | 27 (43.5%) | |||
Other | 3 (4.8%) | |||
Laterality | ||||
Right | 32 (51.6%) | 0.806 | 0.632 | 0.075 |
Left | 30 (48.4%) | |||
Pathological stage | ||||
Stage I | 36 (59.0%) | 0.321 | 0.037 * | 0.051 |
Stage II | 22 (36.1%) | |||
Stage III | 3 (4.9%) | |||
Histological grade | ||||
Grade I Grade II | 0 (0%) 37 (59.7%) | 0.227 | <0.001 * | <0.001 * |
Grade III | 25 (40.3%) | |||
Carcinoma in situ | ||||
Presence | 24 (38.7%) | 0.469 | 0.282 | 0.357 |
Size. cm (mean ± SD) | 1.35 ± 2.47 | 0.649 | 0.798 | 0.463 |
Extensive | 20 (32.3%) | 0.472 | 0.367 | 0.253 |
Microcalcifications | 28 (45.2%) | 0.818 | 0.236 | 0.333 |
Necrosis | 39 (62.9%) | 0.946 | 0.042 * | 0.126 |
Invasive carcinoma | ||||
Size. cm (mean ± SD) | 1.76 ± 0.75 | 0.465 | 0.197 | 0.210 |
Multifocal | 14 (22.6%) | 0.891 | 0.564 | 0.656 |
Invasion | 19 (30.6%) | 0.511 | 0.661 | 0.783 |
Metastatic nodes | ||||
0 | 41 (66.2%) | 0.364 | 0.144 | 0.082 |
1–3 | 18 (29.0%) | |||
4–9 | 1 (1.6%) | |||
>10 | 2 (3.2%) | |||
Size cm (mean ± SD) (Larger metastasis) | 11.48 ± 31.49 | 0.764 | 0.056 | 0.340 |
HK | PFK | PK | PC | PCK | FBP | G6P | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
r | p | r | p | r | p | r | p | r | p | r | p | r | p | |
BMI | −0.147 | 0.275 | −0.162 | 0.229 | −0.059 | 0.650 | −0.303 | 0.021 * | −0.138 | 0.305 | 0.138 | 0.305 | 0.047 | 0.720 |
ER | −0.151 | 0.268 | −0.177 | 0.192 | −0.168 | 0.196 | −0.514 | <0.001 * | −0.284 | 0.034 * | 0.463 | <0.001 * | 0.020 | 0.881 |
PR | −0.151 | 0.268 | −0.177 | 0.192 | −0.168 | 0.196 | −0.514 | <0.001 * | −0.284 | 0.034 * | 0.463 | <0.001 * | 0.020 | 0.881 |
HER2 | 0.277 | 0.039 * | 0.259 | 0.054 | 0.139 | 0.285 | 0.503 | <0.001 * | 0.569 | <0.001 * | −0.075 | 0.580 | 0.059 | 0.658 |
Ki67 | −0.045 | 0.799 | 0.122 | 0.486 | 0.123 | 0.463 | 0.089 | 0.604 | 0.288 | 0.093 | −0.038 | 0.829 | 0.009 | 0.956 |
TL | 0.043 | 0.752 | 0.185 | 0.169 | 0.132 | 0.306 | 0.105 | 0.433 | −0.141 | 0.296 | −0.209 | 0.119 | −0.209 | 0.110 |
LAT | −0.086 | 0.524 | 0.113 | 0.401 | 0.131 | 0.312 | −0.084 | 0.529 | −0.028 | 0.834 | 0.156 | 0.246 | −0.046 | 0.726 |
pST | 0.053 | 0.698 | 0.138 | 0.310 | 0.263 | 0.041 * | 0.437 | <0.001 * | 0.185 | 0.172 | −0.215 | 0.111 | 0.154 | 0.246 |
HG | 0.078 | 0.566 | 0.106 | 0.434 | 0.120 | 0.353 | 0.452 | <0.001 * | 0.238 | 0.075 | −0.396 | 0.002 * | 0.014 | 0.918 |
HGnc | 0.117 | 0.384 | 0.198 | 0.139 | 0.137 | 0.287 | 0.249 | 0.060 | 0.193 | 0.149 | −0.304 | 0.021 * | 0.059 | 0.656 |
HGm | 0.050 | 0.711 | 0.032 | 0.812 | 0.034 | 0.796 | 0.392 | 0.002 * | 0.272 | 0.041 * | −0.320 | 0.015 * | −0.007 | 0.955 |
HGtf | −0.083 | 0.541 | −0.021 | 0.875 | 0.090 | 0.489 | 0.243 | 0.066 | 0.036 | 0.793 | −0.144 | 0.286 | −0.020 | 0.881 |
ISs | −0.016 | 0.906 | −0.120 | 0.373 | −0.094 | 0.469 | −0.071 | 0.595 | −0.151 | 0.263 | 0.088 | 0.514 | 0.230 | 0.077 |
ISext | 0.026 | 0.846 | −0.027 | 0.840 | −0.063 | 0.624 | −0.166 | 0.212 | −0.173 | 0.198 | 0.142 | 0.293 | 0.212 | 0.194 |
ISmc | 0.122 | 0.365 | −0.082 | 0.546 | −0.187 | 0.146 | −0.148 | 0.267 | −0.143 | 0.289 | 0.183 | 0.172 | 0.063 | 0.631 |
ISnec | 0.154 | 0.254 | 0.098 | 0.468 | −0.091 | 0.483 | 0.196 | 0.139 | 0.025 | 0.854 | 0.032 | 0.813 | 0.026 | 0.842 |
INVs | −0.016 | 0.907 | 0.043 | 0.753 | 0.155 | 0.229 | 0.242 | 0.067 | 0.055 | 0.683 | −0.237 | 0.075 | 0.210 | 0.108 |
INVm | 0.234 | 0.080 | −0.137 | 0.309 | −0.053 | 0.680 | −0.031 | 0.816 | 0.014 | 0.918 | −0.014 | 0.920 | 0.109 | 0.407 |
INVvi | 0.269 | 0.043 * | 0.160 | 0.234 | 0.094 | 0.467 | 0.077 | 0.567 | −0.027 | 0.840 | −0.012 | 0.930 | 0.059 | 0.656 |
METs | −0.090 | 0.504 | 0.089 | 0.509 | −0.093 | 0.474 | 0.048 | 0.720 | −0.154 | 0.253 | 0.009 | 0.947 | 0.076 | 0.564 |
Enzymes | χ2 Test | Spearman Correlation | |
---|---|---|---|
p-Value | R | p-Value | |
HK | 0.635 | −0.038 | 0.784 |
PFK | 0.509 | −0.054 | 0.690 |
PK | 0.318 | −0.113 | 0.403 |
PC | 0.580 | 0.035 | 0.796 |
PCK | 0.590 | −0.111 | 0.415 |
FBP | 0.222 | −0.190 | 0.160 |
G6P | 0.569 | −0.049 | 0.718 |
Enzymes | χ2 Test | Spearman Correlation | |
---|---|---|---|
p-Value | r | p-Value | |
HK | 0.411 | 0.209 | 0.126 |
PFK | 0.739 | 0.117 | 0.391 |
PK | 0.264 | −0.017 | 0.900 |
PC | <0.001 * | 0.248 | 0.062 |
PCK | 0.411 | 0.179 | 0.186 |
FBP | 0.465 | −0.071 | 0.604 |
G6P | 0.938 | 0.097 | 0.471 |
n (%) | Total | p-Value BMI Analysis | p-Value MS Analysis | p-Value mBMI Analysis |
---|---|---|---|---|
62 (100.0%) | ||||
Diabetes | ||||
Yes | 7 (11.5%) | 0.589 | 0.883 | 0.791 |
No | 54 (88.5%) | |||
Hypertension | ||||
Yes | 25 (41.0%) | 0.008 * | 0.949 | 0.088 |
No | 36 (59.0%) | |||
Dyslipidemia | ||||
Yes | 39 (63.9%) | 0.175 | 0.495 | 0.549 |
No | 22 (36.1%) |
Enzymes | Diabetes | Hypertension | Dyslipidemia | |||
---|---|---|---|---|---|---|
r | p-Value | r | p-Value | r | p-Value | |
HK | −0.131 | 0.337 | −0.065 | 0.635 | 0.079 | 0.564 |
PFK | 0.070 | 0.607 | 0.177 | 0.187 | 0.180 | 0.180 |
PK | −0.099 | 0.447 | 0.025 | 0.849 | 0.029 | 0.822 |
PC | −0.035 | 0.794 | −0.142 | 0.287 | 0.040 | 0.768 |
PCK | 0.304 | 0.022 * | 0.189 | 0.159 | 0.157 | 0.244 |
FBP | 0.057 | 0.676 | 0.320 | 0.015 * | 0.328 | 0.013 * |
G6P | 0.240 | 0.065 | 0.082 | 0.531 | 0.149 | 0.257 |
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Luís, C.; Schmitt, F.; Fernandes, R.; Coimbra, N.; Rigor, J.; Dias, P.; Leitão, D.; Fernandes, R.; Soares, R. Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes—Obesity as a Crucial Player. Cancers 2023, 15, 4936. https://doi.org/10.3390/cancers15204936
Luís C, Schmitt F, Fernandes R, Coimbra N, Rigor J, Dias P, Leitão D, Fernandes R, Soares R. Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes—Obesity as a Crucial Player. Cancers. 2023; 15(20):4936. https://doi.org/10.3390/cancers15204936
Chicago/Turabian StyleLuís, Carla, Fernando Schmitt, Rute Fernandes, Nuno Coimbra, Joana Rigor, Paula Dias, Dina Leitão, Rúben Fernandes, and Raquel Soares. 2023. "Breast Cancer Molecular Subtypes Differentially Express Gluconeogenic Rate-Limiting Enzymes—Obesity as a Crucial Player" Cancers 15, no. 20: 4936. https://doi.org/10.3390/cancers15204936