Systems biology network reveals the correlation between COX-2 expression and Ch 7q copy number alterations in Ch 11q-deleted pediatric neuroblastoma tumors
Thatyanne Gradowski Farias da Costa do Nascimento1, Mateus Eduardo de Oliveira Thomazini1,2, Nilton de França Junior1, Lisiane de Castro Poncio3, Aline Simoneti Fonseca3, Bonald Cavalcante de Figueiredo3, Saulo Henrique Weber4, Roberto Hirochi Herai1,5, Lucia de Noronha1, Luciane R. Cavalli3,6, Bruno César Feltes7,8, Selene Elifio-Esposito1
1 Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
2 Biotechnology Undergraduate Program. School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
3 Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, PR, Brazil
4 Graduate Program in Animal Science, School of Medicine and Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil
5 Research Department, Instituto Buko Kaesemodel (IBK), Curitiba, Paraná, Brazil
6 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA
7 Institute of Informatics, Department of Theoretical Informatics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
8 Institute of Biosciences, Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
Correspondence:
Selene Elifio-Esposito, email:[email protected]
Keywords: pediatric cancer; inflammation; chromosomal aberration; interaction network; neuroblastoma
Received: June 02, 2022 Accepted: November 18, 2022 Published: December 02, 2022
Abstract
Tumor-associated inflammation and chromosomal aberrations can play crucial roles in cancer development and progression. In neuroblastoma (NB), the enzyme cyclooxygenase-2 (COX-2) is associated with copy number alterations on the long arm of chromosome 11 (Ch 11q), defining an aggressive disease subset. This retrospective study included formalin-fixed paraffin-embedded tumor samples collected from nine patients during diagnosis at the pediatric Pequeno Principe Hospital, Curitiba, PR, Brazil, and post-chemotherapy (CT). COX-2 expression was evaluated using immunohistochemistry and correlated with the genome profile of paired pre- and post-CT samples, determined by array comparative genomic hybridization. A systems biology approach elucidated the PTGS2 network interaction. The results showed positive correlations between pre-CT Ch 7q gain and COX-2 expression (ρ = 0.825; p-value = 0.006) and negative correlations between Ch 7q gain and Ch 11q deletion (ρ = −0.919; p-value = 0.0005). Three samples showed Ch 11q deletion and Ch 7q gain. Network analysis identified a direct connection between CAV-1 (Ch 7q) and COX-2 in NB tumors and highlighted the connection between amplified genes in Ch 7q and deleted ones in 11q. The identification of hub-bottleneck-switch genes provides new biological insights into this connection between NB, tumorigenesis, and inflammation.
