The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology
Abstract
:1. Introduction
2. Results
2.1. High Fat Diet-Induced Visceral Obesity in BD/II Han Rats
2.2. Diet-Induced Obesity Did Not Increase the Endometrial Cancer Burden in BDII/Han Rats
2.3. Diet-Induced Obesity Caused Specific Transcriptomic Changes in BDII/Han Endometrial Tumours
2.4. Obesity-Regulated Genes Can Be Used as Biomarkers in Human Endometrial Cancer
2.5. Mutation and Expression of Tp53, Molecular Characterisation
3. Discussion
4. Materials and Methods
4.1. CT Imaging
4.2. Assessment of Endometrial Cancer Burden
4.3. Retrieval of Endometrial Tissue for Histology and RNA Isolation
4.4. RNA Extraction, Library Prep and Sequencing
4.5. RNAseq Processing, Differential Expression Analysis and Variant Calling
4.6. Pathway and Functional Enrichment Analysis
4.7. TCGA Comparative Model
4.8. Ethics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Appendix A
RNA Extraction, Library Prep and Sequencing
References
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A2M Low (n = 191) | A2M High (n = 180) | p-Value | Crabp2 Low (n = 265) | Crabp2 High (n = 106) | p-Value | |
---|---|---|---|---|---|---|
Age Median (range) | 63 (35–90) | 63 (31–90) | 0.665 | 63 (33–90) | 65 (31–90) | 0.093 * |
BMI Median (range) | 33.1 (19–82) | 32.3 (17–61) | <0.001 * | 33 (17–82) | 31 (19–68) | 0.485 * |
Histology | ||||||
Endometrioid | 147 (77) | 158 (87) | 0.003 | 238(90) | 67 (63) | <0.001 |
Serous | 32 (16.7) | 21 (12) | 20 (7) | 33 (31) | ||
Mixed | 12 (6.3) | 1 (1) | 7 (3) | 6 (6) | ||
Stage | ||||||
1 | 120 (63.1) | 132(74.2) | 0.15 | 194 (74) | 59 (55) | 0.005 |
2 | 16 (8.4) | 10 (5) | 16 (6) | 10 (9) | ||
3 | 44 (23.1) | 30 (16.8) | 47 (18) | 28 (26) | ||
4 | 11 (5.4) | 8 (4) | 8 (2) | 9 (9) | ||
Grade | ||||||
1 | 31 (16.2) | 58 (32.2) | <0.001 | 74 (28) | 15 (14) | 0.001 |
2 | 50 (26.1) | 55 (30.5) | 77 (29) | 28 (26) | ||
3 | 110 (57.7) | 67 (37.3) | 114 (43) | 63 (59) | ||
TCGA molecular subtype | ||||||
POLE | 11 (10.2) | 6 (4.8) | 0.28 | 16 (10) | 1 (2) | <0.001 |
MSI | 30 (28) | 35 (28) | 58 (35) | 7 (10) | ||
CN Low | 32 (30) | 58 (46.4) | 65 (39) | 25 (37) | ||
CN High | 34 (31.8) | 26 (20.8) | 26 (16) | 34 (51) |
Univariate | Multivariate | |||||||
---|---|---|---|---|---|---|---|---|
HR | 95.0% CI | p-Value | HR | 95.0% CI | p-Value | |||
Overall Survival | Lower | Upper | Lower | Upper | ||||
A2M (low vs. high) | 0.455 | 0.23 | 0.9 | 0.024 | 0.612 | 0.305 | 1.229 | 0.167 |
Age (continuous) | 1.041 | 1.009 | 1.075 | 0.013 | 1.053 | 1.015 | 1.092 | 0.005 |
Histology (endometrioid vs. non-endometrioid | 2.298 | 1.18 | 4.475 | 0.014 | 0.705 | 0.311 | 1.595 | 0.401 |
Stage (1 and 2 vs. 3 and 4) | 4.654 | 2.448 | 8.849 | <0.001 | 3.912 | 1.903 | 8.042 | <0.001 |
Grade (1 and 2 vs. 3) | 3.393 | 1.652 | 6.969 | 0.001 | 1.848 | 0.796 | 4.289 | 0.153 |
HR | 95.0% CI | p-Value | HR | 95.0% CI | p-Value | |||
Overall Survival | Lower | Upper | Lower | Upper | ||||
Crabp2 (low vs. high) | 3.554 | 1.875 | 6.735 | <0.001 | 3.134 | 1.524 | 6.443 | 0.002 |
Age (continuous) | 1.041 | 1.009 | 1.075 | 0.013 | 1.046 | 1.011 | 1.083 | 0.01 |
Histology (endometrioid vs. non-endometrioid) | 2.298 | 1.18 | 4.475 | 0.014 | 0.451 | 0.193 | 1.052 | 0.065 |
Stage (1 and 2 vs. 3 and 4) | 4.654 | 2.448 | 8.849 | <0.001 | 3.875 | 1.868 | 8.036 | <0.001 |
Grade (1 and 2 vs. 3) | 3.393 | 1.652 | 6.969 | 0.001 | 1.802 | 0.775 | 4.19 | 0.171 |
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Wilkinson, M.; Sinclair, P.; Dellatorre-Teixeira, L.; Swan, P.; Brennan, E.; Moran, B.; Wedekind, D.; Downey, P.; Sheahan, K.; Conroy, E.; et al. The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology. Life 2020, 10, 188. https://doi.org/10.3390/life10090188
Wilkinson M, Sinclair P, Dellatorre-Teixeira L, Swan P, Brennan E, Moran B, Wedekind D, Downey P, Sheahan K, Conroy E, et al. The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology. Life. 2020; 10(9):188. https://doi.org/10.3390/life10090188
Chicago/Turabian StyleWilkinson, Michael, Piriyah Sinclair, Ludmilla Dellatorre-Teixeira, Patrick Swan, Eoin Brennan, Bruce Moran, Dirk Wedekind, Paul Downey, Kieran Sheahan, Emer Conroy, and et al. 2020. "The Molecular Effects of a High Fat Diet on Endometrial Tumour Biology" Life 10, no. 9: 188. https://doi.org/10.3390/life10090188