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High B7-H3 protein expression in Medulloblastoma is associated with metastasis and unfavorable patient outcomes
Patrícia Fontão1,2,3, Gustavo Ramos Teixeira4,5, Daniel Antunes Moreno1
1Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP, 14784-400, Brazil.
Background:
Medulloblastoma (MB) is the most common malignant brain tumor in children. Although the 5-year survival rate is approximately 70-80%, the current standard treatment results in severe and long-term side effects. The search for new anticancer immunotherapeutic targets has identified B7-H3 as a promising candidate in various solid tumors. However, the role of B7-H3 in MB remains unclear, and studies reporting its protein expression and association with clinicopathological characteristics are still limited.
Methods:
In this study, B7-H3 protein expression was evaluated by immunohistochemistry in seven non-tumor samples and 43 molecularly characterized MB tissues. Its expression profile was correlated with B7-H3 (CD276) mRNA levels, which were previously determined by nCounter, as well as with the patients' clinical features.
Results:
Only 14.3% (1/7) of non-tumor brain and cerebellum tissues showed B7-H3 positivity, whereas 95.6% (41/43) of the MB samples expressed this protein at distinct levels. B7-H3 was found in the cytoplasm and on the membrane of cancer cells. A significant positive correlation was observed between CD276 mRNA and B7-H3 protein levels. Moreover, high expression of B7-H3 protein was associated with worse overall survival and the presence of metastasis at diagnosis.
Conclusions:
This is the first study to associate CD276 mRNA and B7-H3 protein levels in MB, revealing a significant positive correlation. We observed that B7-H3 was overexpressed in MB compared to non-tumor brain tissue. High B7-H3 expression was associated with a worse outcome and with the presence of metastasis at diagnosis.
Insights
B7-H3 protein is highly expressed in pediatric medulloblastoma (MB) and linked to poorer survival and metastasis. This finding highlights B7-H3 as a potential therapeutic target for this common childhood brain cancer.
Area of Science:
- Pediatric oncology
- Neuro-oncology
- Cancer immunology
Background:
- Medulloblastoma (MB) is the most common pediatric malignant brain tumor.
- Current treatments cause severe long-term side effects.
- B7-H3 is a potential immunotherapeutic target in solid tumors, but its role in MB is unclear.
Purpose of the Study:
- To investigate B7-H3 protein expression in medulloblastoma.
- To correlate B7-H3 expression with mRNA levels and clinicopathological features.
- To assess the potential of B7-H3 as a therapeutic target in MB.
Main Methods:
- Immunohistochemistry used to evaluate B7-H3 protein expression in 43 MB tissues and 7 non-tumor samples.
- B7-H3 protein levels correlated with CD276 (B7-H3) mRNA levels.
- Expression profile analyzed against patient clinical features.
Main Results:
- B7-H3 protein was expressed in 95.6% of MB samples, versus 14.3% of non-tumor tissues.
- A significant positive correlation was found between CD276 mRNA and B7-H3 protein levels.
- High B7-H3 expression correlated with worse overall survival and presence of metastasis.
Conclusions:
- B7-H3 is significantly overexpressed in medulloblastoma compared to normal brain tissue.
- This study establishes a correlation between CD276 mRNA and B7-H3 protein levels in MB.
- High B7-H3 expression is associated with adverse outcomes, indicating its potential as a therapeutic target.
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