Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Patient Population
2.2. Pathologic Assessment of Hematoxylin and Eosin (H&E)-Stained Tumor Slides and RNA Extraction
2.3. RNA Sequencing
2.4. Bioinformatic Analysis
2.5. Statistical Analysis
3. Results
3.1. Patient and Tumor Characteristics
3.2. De Novo Metastasized (dnMBC) and Non-Metastasized Breast Tumors (eBC) Exhibit Comparable Cellular Composition
3.3. Gene Expression Signatures Did Not Differ between De Novo Versus Non-Metastasized Tumors
3.4. Tumor Microenvironment Differs at the Time of Diagnosis
3.4.1. Hypoxia Pathways Are Upregulated in De Novo Metastasized Tumors
3.4.2. De Novo Metastasis Is Associated with an Altered Immune Landscape
3.4.3. Numerous Regulatory Genes Are Affected in the De Novo Metastasized Tumors
4. Discussion
5. Limitations of the Study
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Statistics | De Novo Metastasized BC Group (dnMBC) | Non-Primary Metastasized BC Group (eBC) | p-Values |
---|---|---|---|---|
Age patients | 0.532 | |||
N | 32 | 32 | ||
Median | 62 | 61 | ||
Average | 61.69 | 60.84 | ||
Range | [32.0; 88.0] | [36.0; 83.0] | ||
Grade of tumor | 1.000 | |||
Grade 2 | n/N (%) | 14/32 (44%) | 15/32 (47%) | |
Grade 3 | n/N (%) | 18/32 (56%) | 17/32 (53%) | |
Receptor status | 0.672 | |||
ER+/HER2−/PR+ | n/N (%) | 28/32 (87%) | 30/32 (94%) | |
ER+/HER2−/PR− | n/N (%) | 4/32 (13%) | 2/32 (6%) | |
Clinical staging (cT) | 0.009 | |||
cT1 | n/N (%) | 1/32 (3%) | 6/32 (19%) | |
cT2 | n/N (%) | 17/32 (53%) | 23/32 (72%) | |
cT3 | n/N (%) | 4/32 (13%) | 3/32 (9%) | |
cT4 | n/N (%) | 10/32 (31%) | 0/32 (0%) | |
cT4b | n/N (%) | 3/32 (9%) | 0/32 (0%) | |
cT4c | n/N (%) | 1/32 (3%) | 0/32 (0%) | |
cT4d | n/N (%) | 5/32 (16%) | 0/32 (0%) | |
Lymph node involvement (cN) | <0.001 | |||
cN0 | n/N (%) | 6/32 (19%) | 21/32 (66%) | |
cN1 | n/N (%) | 11/32 (34%) | 11/32 (34%) | |
cN2 | n/N (%) | 3/32 (9%) | 0/32 (0%) | |
cN3 | n/N (%) | 12/32 (38%) | 0/32 (0%) | |
Tumor size (mm) | <0.001 | |||
Median | 37 | 27 | ||
Average | 43.68 | 28.47 | ||
Range | [16.0; 140.0] | [15.0; 55.0] | ||
Location of metastasis | - | |||
Brain | n/N (%) | 0/32 (0%) | - | |
AbdominalNonLiver | n/N (%) | 3/32 (9%) | - | |
Liver | n/N (%) | 13/32 (41%) | - | |
Cutaneous | n/N (%) | 3/32 (9%) | - | |
Lung | n/N (%) | 11/32 (34%) | - | |
Bone | n/N (%) | 21/32 (66%) | - | |
Locoregional lymph nodes | n/N (%) | 12/32 (38%) | - | |
Others | n/N (%) | 1/32 (3%) | - |
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Lambrechts, Y.; Hatse, S.; Richard, F.; Boeckx, B.; Floris, G.; Desmedt, C.; Smeets, A.; Neven, P.; Lambrechts, D.; Wildiers, H. Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors. Cancers 2023, 15, 4341. https://doi.org/10.3390/cancers15174341
Lambrechts Y, Hatse S, Richard F, Boeckx B, Floris G, Desmedt C, Smeets A, Neven P, Lambrechts D, Wildiers H. Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors. Cancers. 2023; 15(17):4341. https://doi.org/10.3390/cancers15174341
Chicago/Turabian StyleLambrechts, Yentl, Sigrid Hatse, François Richard, Bram Boeckx, Giuseppe Floris, Christine Desmedt, Ann Smeets, Patrick Neven, Diether Lambrechts, and Hans Wildiers. 2023. "Differences in the Tumor Molecular and Microenvironmental Landscape between Early (Non-Metastatic) and De Novo Metastatic Primary Luminal Breast Tumors" Cancers 15, no. 17: 4341. https://doi.org/10.3390/cancers15174341