Novo biomarcador de prognóstico em meduloblastoma

Recentemente, dados de 2022 mostraram que Portugal regista a taxa mais elevada de incidência de cancro infantil na União Europeia, sendo o meduloblastoma o tumor cerebral maligno mais comum diagnosticado em crianças. O tratamento padrão para este tipo tumoral consiste em cirurgia, radioterapia e quimioterapia, no entanto não é eficaz em todos os casos e causa efeitos secundários graves a longo-termo. A investigação de novos alvos terapêuticos identificou a proteína B7-H3 como um candidato promissor em vários tipos de tumores. O nosso grupo identificou previamente que o gene que codifica esta proteína está aumentado no tumor dos pacientes com meduloblastoma. Assim, neste estudo avaliamos a expressão desta proteína numa série de casos de meduloblastoma, tendo confirmado a sua alta expressão comparativamente ao tecido cerebral normal. Adicionalmente, observámos que a alta expressão da proteína nos tumores destes pacientes está associada a um pior prognóstico e com a presença de metástases no diagnóstico. Estes dados suportam o papel desta proteína como um potencial novo marcador de prognóstico e agressividade tumoral em meduloblastoma.

Autores e Afiliações:
Patrícia Fontão^1,2,3, Gustavo Ramos Teixeira^4,5, Daniel Antunes Moreno¹, Rui Ferreira Marques^2,3, João Norberto Stavale⁶, Suzana Maria Fleury Malheiros⁶, Carlos Almeida Júnior⁷, Bruna Minniti Mançano¹ and Rui Manuel Reis^1,2,3

¹Molecular Oncology Research Center, Barretos Cancer Hospital, Rua Antenor Duarte Vilela, 1331, Barretos, SP 14784-400, Brazil

²Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

³ICVS/3Bs-PT Government Associate Laboratory, Braga/Guimarães, Portugal

⁴Barretos School of Health Sciences, Dr. Paulo Prata – FACISB, Barretos, São Paulo, Brazil

⁵Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

⁶Federal University of São Paulo, São Paulo, Brazil

⁷Barretos Children’s Cancer Hospital, Barretos, Brazil

Abstract:
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.

Revista: Diagnostic Pathology

Link: https://link.springer.com/article/10.1186/s13000-025-01645-y