Article
Metastatic markers as potential targets for the treatment of glioblastoma
Metastasenmarker als potenzielle Ziele für die Behandlung von Glioblastomen
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Published: | May 25, 2022 |
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Objective: Metastasis from solid tumors is often associated with the expression of specific molecules such as S100A4, MACC1, CD44, and E- and N-cadherin. In particular, S100A4, a transmembrane protein, appears to be a key molecule in the development of distant metastases. This, as well as E- and N-cadherin, MACC1, is involved in intracellular processes such as epithelial-mesenchymal transition (EMT). We investigated to what extent these factors play a role in intracerebral metastases compared to brain-derived tumors.
Methods: RNA was isolated from samples of patients with intracerebral metastases from pulmonary carcinoma (n=32), colon carcinoma (n=7), rectal carcinoma (n=14), renal cell carcinoma (n=5), and intracerebral melanoma (n=11). In addition, 22 samples from glioblastoma (GBM) patients were processed. Quantitative polymerase chain reaction (qPCR) was performed to determine the expression of the genes S100A4, MACC1, CDH1 as well as CDH2. The analysis was performed using the efficiency-based delta delta Ct method according to Pfaffl and subsequent statistical analysis (Mann-Whitney U test).
Results: All investigated genes were strongly expressed in all study groups. Comparative analysis revealed significantly higher expression levels in intracerebral metastases compared to glioblastomas. Thereby, the highest S100A4 expressions were found in the samples of renal cell carcinoma metastases (R=18.8; p=0.001) and bronchial carcinoma metastases (R=6.3; p=0.001) compared to GBM. The highest MACC1 expressions were found in colorectal carcinoma metastases (R=6.6; p=0.006) and renal cell carcinoma metastases (R=30.8; p=0.000). But, similar expressions in comparison to GBM showed melanoma metastases (R=1.4) and bronchial carcinoma metastases (R=1.5) for MACC1. Additionally, significantly higher relative expressions were detected for CDH1 and significantly lower relative expressions were detected for CDH2 in the intracerebral metastases compared to the brain-derived tumors.
Conclusion: S100A4, which is thought to play a key role in the formation of distant metastases, and MACC1 were more strongly expressed in most of the metastatic types studied. However, strong absolute expression was also detected for gliolastomas. MACC1 in particular features prominently due to similarities in expression levels between gliobastomas and intracerebral metastases. Thus, S100A4 and/or MACC1 could represent a potential therapeutic target.