Comprehensive Characterization of the Regulatory Landscape of Adrenocortical Carcinoma: Novel Transcription Factors and Targets Associated with Prognosis.

Muzzi, João C D; Magno, Jéssica M; Souza, Jean S; Alvarenga, Larissa M; de Moura, Juliana F; Figueiredo, Bonald C; Castro, Mauro A A

Muzzi, João C D; Magno, Jéssica M; Souza, Jean S; Alvarenga, Larissa M; de Moura, Juliana F; Figueiredo, Bonald C; Castro, Mauro A A.

Afiliação

Muzzi JCD; Laboratório de Imunoquímica (LIMQ), Pós-Graduação em Microbiologia, Parasitologia e Patologia, Departamento de Patologia Básica, Universidade Federal do Paraná (UFPR), Curitiba 81530-990, Brazil.
Magno JM; Laboratório de Bioinformática e Biologia de Sistemas, Pós-Graduação em Bioinformática, Universidade Federal do Paraná (UFPR), Curitiba 81520-260, Brazil.
Souza JS; Oncology Division, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, Brazil.
Alvarenga LM; Laboratório de Bioinformática e Biologia de Sistemas, Pós-Graduação em Bioinformática, Universidade Federal do Paraná (UFPR), Curitiba 81520-260, Brazil.
de Moura JF; Oncology Division, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, Brazil.
Figueiredo BC; Oncology Division, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba 80250-060, Brazil.
Castro MAA; Laboratório de Imunoquímica (LIMQ), Pós-Graduação em Microbiologia, Parasitologia e Patologia, Departamento de Patologia Básica, Universidade Federal do Paraná (UFPR), Curitiba 81530-990, Brazil.

Cancers (Basel) ; 14(21)2022 Oct 27.

Article em En | MEDLINE | ID: mdl-36358698

RESUMO

We reconstructed a transcriptional regulatory network for adrenocortical carcinoma (ACC) using transcriptomic and clinical data from The Cancer Genome Atlas (TCGA)-ACC cohort. We investigated the association of transcriptional regulatory units (regulons) with overall survival, molecular phenotypes, and immune signatures. We annotated the ACC regulons with cancer hallmarks and assessed single sample regulon activities in the European Network for the Study of Adrenal Tumors (ENSAT) cohort. We found 369 regulons associated with overall survival and subdivided them into four clusters: RC1 and RC2, associated with good prognosis, and RC3 and RC4, associated with worse outcomes. The RC1 and RC3 regulons were highly correlated with the 'Steroid Phenotype,' while the RC2 and RC4 regulons were highly correlated with a molecular proliferation signature. We selected two regulons, NR5A1 (steroidogenic factor 1, SF-1) and CENPA (Centromeric Protein A), that were consistently associated with overall survival for further downstream analyses. The CENPA regulon was the primary regulator of MKI-67 (a marker of proliferation KI-67), while the NR5A1 regulon is a well-described transcription factor (TF) in ACC tumorigenesis. We also found that the ZBTB4 (Zinc finger and BTB domain-containing protein 4) regulon, which is negatively associated with CENPA in our transcriptional regulatory network, is also a druggable anti-tumorigenic TF. We anticipate that the ACC regulons may be used as a reference for further investigations concerning the complex molecular interactions in ACC tumors.

Palavras-chave

CENPA; IZKF1; KI-67; NR5A1; ZBTB4; adrenocortical carcinoma; immuno-oncology; regulatory network; transcription factor; transcriptomics

Texto completo

Adicionar na Minha BVS

Imprimir

XML

PubMed Links

Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Cancers (Basel) Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça

Texto completo

Adicionar na Minha BVS

Imprimir

XML

PubMed Links

Buscar no Google