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Integrative analysis reveals an indirect connection between COX-2/PTGS2 and extracellular matrix proteins in Ch11q-deleted neuroblastoma
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  • Thatyanne Gradowski Farias da Costa do Nascimento,
  • Nilton de França Júnior,
  • Lisiane de Castro Poncio,
  • Aline Simoneti Fonseca,
  • Bonald Figueiredo,
  • Saulo Henrique Weber,
  • Roberto Hirochi Herai,
  • Lucia de Noronha,
  • Luciane Cavalli,
  • Bruno César Feltes,
  • Selene Esposito
Thatyanne Gradowski Farias da Costa do Nascimento
Pontifícia Universidade Católica do Paraná
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Nilton de França Júnior
Pontifícia Universidade Católica do Paraná
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Lisiane de Castro Poncio
Instituto de Pesquisa Pelé Pequeno Príncipe
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Aline Simoneti Fonseca
Instituto de Pesquisa Pelé Pequeno Príncipe
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Bonald Figueiredo
Instituto de Pesquisa Pelé Pequeno Príncipe
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Saulo Henrique Weber
Pontifícia Universidade Católica do Paraná
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Roberto Hirochi Herai
Pontifícia Universidade Católica do Paraná
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Lucia de Noronha
Pontifícia Universidade Católica do Paraná
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Luciane Cavalli
Instituto de Pesquisa Pelé Pequeno Príncipe
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Bruno César Feltes
Universidade Federal do Rio Grande do Sul
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Selene Esposito
Pontifícia Universidade Católica do Paraná
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Abstract

The COX-2 protein, encoded by the PTGS2 gene, is related to tumor progression in adult and pediatric cancer. In neuroblastoma (NB), COX-2 was associated with loss of heterozygosity on the long arm of chromosome 11 (Ch11q loss of heterozygosity, LOH), defining a subset of aggressive disease. The present study aimed to investigate the protein expression of COX-2 in a set of 82 pre-chemotherapy (CT) and 20 post-CT NB specimens and its correlation with clinical and genomic data. A systems biology approach elucidated the network interaction of PTGS2 and other inflammation-related genes with those codified in the Ch11q deleted regions. The results indicated a significantly higher expression of COX-2 in post-CT samples. In addition, a significant positive correlation between the presence of aberrations in Ch11q and COX-2 levels and an indirect connection between the COX-2 gene and extracellular matrix remodeling (ECM)-related proteins were observed. Our findings suggest that deregulation of ECM proteolysis in Ch11q–deleted NB could elicit stromal alterations, triggering inflammatory responses via COX-2 overexpression, ultimately supporting NB progression.