Identifying prognostic hub genes and key pathways in pediatric adrenocortical tumors through RNA sequencing and Co-expression analysis

• Published in: Molecular and cellular endocrinology 2024-12, Vol.594, p.112383, Article 112383
• Main Authors: Veronez, Luciana Chain, Xavier, Alcides Euzebio Tavares, Nagano, Luiz Fernando, Correa, Carolina Alves Pereira, Borges, Kleiton Silva, Santos, Paula, Baroni, Mirella, Silva Queiroz, Rosane de Paula, Antonini, Sonir Roberto Rauber, Yunes, José Andres, Brandalise, Silvia Regina, Molina, Carlos Augusto Fernandes, Pinto, Emilia Modolo, Valera, Elvis Terci, Tone, Luiz Gonzaga, Scrideli, Carlos Alberto
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Cortex Neoplasms - genetics; Adrenal Cortex Neoplasms - mortality; Adrenocortical Carcinoma - genetics; Adrenocortical Carcinoma - mortality; Adrenocortical Carcinoma - pathology; Biomarkers, Tumor - genetics; Child; Child, Preschool; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; hub genes; Humans; Infant; Male; pediatric adrenocortical tumor; Prognosis; Sequence Analysis, RNA - methods; Transcriptome - genetics
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2024.112383

Pediatric adrenocortical tumors (ACTs), rare conditions with uncertain prognoses, have high incidence in southern and southeastern Brazil. Pediatric ACTs are highly heterogeneous, so establishing prognostic markers for these tumors is challenging. We have conducted transcriptomic analysis on 14 pediatric ACT samples and compared cases with favorable and unfavorable clinical outcomes to identify prognostically significant genes. This comparison showed 1257 differentially expressed genes in favorable and unfavorable cases. Among these genes, 15 out of 60 hub genes were significantly associated with five-year event-free survival (EFS), and 10 had significant diagnostic value for predicting ACT outcomes in an independent microarray dataset of pediatric adrenocortical carcinomas (GSE76019). Overexpression of N4BP2, HSPB6, JUN, APBB1IP, STK17B, CSNK1D, and KDM3A was associated with poorer EFS, whereas lower expression of ISCU, PTPR, PRKAB2, CD48, PRF1, ITGAL, KLK15, and HIST1H3J was associated with worse outcomes. Collectively, these findings underscore the prognostic significance of these hub genes and suggest that they play a potential role in pediatric ACT progression and are useful predictors of clinical outcomes. •Pediatric adrenocortical tumors are heterogeneous disease.•Metastatic disease has poor outcome, with an estimated five-year survival rate of less than 20%.•The biological characteristics and behavior of these tumors are not completely understood.•Molecular understanding is essential for identifying potential therapeutic targets and prognostic markers.