MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune-related pathways

Autor(es)

Veronez, Luciana C. ^[1] ; das Chagas, Pablo F. ^[2] ; Correa, Carolina A. P. ^[2] ; Baroni, Mirella ^[2] ; da Silva, Keteryne R. ^[2] ; Nagano, Luis F. ^[2] ; Borges, Kleiton S. ^[3] ; Queiroz, Rosane G. P. ^[1] ; Tone, Luiz G. ^[1] ; Scrideli, Carlos A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[3] Boston Childrens Hosp, Div Endocrinol, Boston, MA - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Biochemistry; v. 122, n. 12 SEP 2021.
• Citações Web of Science: 0

Resumo

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 - 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune-related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC. (AU)

• Processo FAPESP: 18/04477-0 - Estudo das relações entre as vias TGF-beta e Wnt/beta-catenina em Tumores Adrenocorticais
• Beneficiário: Luciana Chain Veronez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/20341-0 - Interação entre alvos terapêuticos emergentes e vias de desenvolvimento associadas à tumorigênese: ênfase em neoplasias da criança e do adolescente
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/26160-5 - Gene Musashi-1 em meduloblastoma de grupo 3 e 4
• Beneficiário: Pablo Shimaoka Chagas
• Modalidade de apoio: Bolsas no Brasil - Doutorado