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| Status |
Public on Dec 03, 2023 |
| Title |
Unlocking Molecular mechanisms and identifying druggable targets in matched-paired brain metastasis of Breast and Lung cancers |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Introduction: The incidence of brain metastases in cancer patients is increasing, with lung and breast cancer being the most common sources. Despite advancements in targeted therapies, the prognosis remains poor, highlighting the importance to investigate the underlying mechanisms in brain metastases. The aim of this study was to investigate the differences in the molecular mechanisms involved in brain metastasis of breast and lung cancers. In addition, we aimed to identify cancer lineage-specific druggable targets in the brain metastasis. Methods: To that aim, a cohort of 44 FFPE tissue samples, including 22 breast cancer and 22 lung adenocarcinoma (LUAD) and their matched-paired brain metastases were collected. Targeted gene expression profiles of primary tumors were compared to their matched-paired brain metastases samples using nCounter PanCancer IO 360™ Panel of NanoString technologies. Pathway analysis was performed using gene set analysis (GSA) and gene set enrichment analysis (GSEA). The validation was performed by using Immunohistochemistry (IHC) to confirm the expression of immune checkpoint inhibitors. Results: Our results revealed the significant upregulation of cancer-related genes in primary tumors compared to their matched-paired brain metastases (adj. p ≤ 0.05). We found that upregulated differentially expressed genes in breast cancer brain metastasis (BM-BC) and brain metastasis from lung adenocarcinoma (BM-LUAD) were associated with the metabolic stress pathway, particularly related to the glycolysis. Additionally, we found that the upregulated genes in BM-BC and BM-LUAD played roles in immune response regulation, tumor growth, and proliferation. Importantly, we identified high expression of the immune checkpoint VTCN1 in BM-BC, and VISTA, IDO1, NT5E, and HDAC3 in BM-LUAD. Validation using immunohistochemistry further supported these findings. Conclusion: In conclusion, the findings highlight the significance of using matched-paired samples to identify cancer lineage-specific therapies that may improve brain metastasis patients outcomes.
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| Overall design |
RNA was extracted from FFPE samples of (primary LUAD and their matched paired brain metastasis n=22, primary BC and their matched paired brain metastasis n=22)
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| Contributor(s) |
Najjary S, de Koning W, Kros JM, Mustafa DA |
| Citation missing |
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| Submission date |
Nov 28, 2023 |
| Last update date |
Dec 03, 2023 |
| Contact name |
Shiva Najjary |
| E-mail(s) |
s.najjary@erasmusmc.nl
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| Organization name |
Erasmus University Medical Center
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| Street address |
Dr. Molewaterplein 40
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| City |
Rotterdam |
| ZIP/Postal code |
3015 GD |
| Country |
Netherlands |
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| Platforms (1) |
| GPL32069 |
NanoString Human nCounter PanCancer IO360 Panel |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA1046077 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248830_Raw_data.csv.gz |
62.4 Kb |
(ftp)(http) |
CSV |
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