Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma

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art_LACOMBE_Sterol_OAcyl_Transferase_1_as_a_Prognostic_Marker_2020.PDF (1.91 MB)
Citações na Scopus
19
Tipo de produção
article
Data de publicação
2020
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
MDPI
Autores
Citação
CANCERS, v.12, n.1, article ID 247, 12p, 2020
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis. Despite the poor prognosis in the majority of patients, no improvements in treatment strategies have been achieved. Therefore, the discovery of new prognostic biomarkers is of enormous interest. Sterol-O-acyl transferase 1 (SOAT1) is involved in cholesterol esterification and lipid droplet formation. Recently, it was demonstrated that SOAT1 inhibition leads to impaired steroidogenesis and cell viability in ACC. To date, no studies have addressed the impact of SOAT1 expression on ACC prognosis and clinical outcomes. We evaluated SOAT1 expression by quantitative real-time polymerase chain reaction and immunohistochemistry in a tissue microarray of 112 ACCs (Weiss score >= 3) from adults treated in a single tertiary center in Brazil. Two independent pathologists evaluated the immunohistochemistry results through a semiquantitative approach (0-4). We aimed to evaluate the correlation between SOAT1 expression and clinical, biochemical and anatomopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS). SOAT1 protein expression was heterogeneous in this cohort, 37.5% of the ACCs demonstrated a strong SOAT1 protein expression (score > 2), while 62.5% demonstrated a weak or absent protein expression (score <= 2). Strong SOAT1 protein expression correlated with features of high aggressiveness in ACC, such as excessive tumor cortisol secretion (p = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 (p = 0.011)] and a high Ki67 index (p = 0.002). In multivariate analysis, strong SOAT1 protein expression was an independent predictor of a reduced OS (hazard ratio (HR) 2.15, confidence interval (CI) 95% 1.26-3.66; p = 0.005) in all patients (n = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; p = 0.027) in patients with localized disease at diagnosis (n = 83). Our findings demonstrated that SOAT1 protein expression has prognostic value in ACC and reinforced the importance of investigating SOAT1 as a possible therapeutic target for patients with ACC.
Palavras-chave
adrenocortical carcinoma, prognostic factors, SOAT1, target therapies
URI
https://observatorio.fm.usp.br/handle/OPI/35858
Referências
  1. Allolio B, 2006, J CLIN ENDOCR METAB, V91, P2027, DOI 10.1210/jc.2005-2639
  2. Beuschlein F, 2015, J CLIN ENDOCR METAB, V100, P841, DOI 10.1210/jc.2014-3182
  3. Chang TY, 2006, ANNU REV CELL DEV BI, V22, P129, DOI 10.1146/annurev.cellbio.22.010305.104656
  4. Duregon E, 2017, HUM PATHOL, V62, P1, DOI 10.1016/j.humpath.2016.09.035
  5. Eisenhauer EA, 2009, EUR J CANCER, V45, P228, DOI 10.1016/j.ejca.2008.10.026
  6. Else T, 2014, ENDOCR REV, V35, P282, DOI 10.1210/er.2013-1029
  7. Fassnacht M, 2013, J CLIN ENDOCR METAB, V98, P4551, DOI 10.1210/jc.2013-3020
  8. Ferraz-de-Souza B, 2011, J CLIN ENDOCR METAB, V96, pE663, DOI 10.1210/jc.2010-2021
  9. Geng F, 2016, CLIN CANCER RES, V22, P5337, DOI 10.1158/1078-0432.CCR-15-2973
  10. Jiang Y, 2019, NATURE, V567, P257, DOI 10.1038/s41586-019-0987-8
  11. Li J, 2016, ONCOGENE, V35, P6378, DOI 10.1038/onc.2016.168
  12. Maan M, 2018, BIOCHEM BIOPH RES CO, V504, P582, DOI 10.1016/j.bbrc.2018.02.097
  13. Petan T, 2018, MOLECULES, V23, DOI 10.3390/molecules23081941
  14. Sbiera S, 2015, ENDOCRINOLOGY, V156, P3895, DOI 10.1210/en.2015-1367
  15. Sbiera S, 2010, J CLIN ENDOCR METAB, V95, pE161, DOI 10.1210/jc.2010-0653
  16. SHI SR, 1991, J HISTOCHEM CYTOCHEM, V39, P741, DOI 10.1177/39.6.1709656
  17. Tirinato L, 2017, STEM CELLS INT, V2017, DOI 10.1155/2017/1656053
  18. Uhlen M, 2017, SCIENCE, V357, P660, DOI 10.1126/science.aan2507
  19. Yue SH, 2014, CELL METAB, V19, P393, DOI 10.1016/j.cmet.2014.01.019

Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/14
Artigos e Materiais de Revistas Científicas - LIM/42
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