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

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-acy...

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Autores principales: Lacombe, Amanda Meneses Ferreira, Soares, Iberê Cauduro, Mariani, Beatriz Marinho de Paula, Nishi, Mirian Yumie, Bezerra-Neto, João Evangelista, Charchar, Helaine da Silva, Brondani, Vania Balderrama, Tanno, Fabio, Srougi, Victor, Chambo, José Luiz, Costa de Freitas, Ricardo Miguel, Mendonca, Berenice Bilharinho, Hoff, Ana O., Almeida, Madson Q., Weigand, Isabel, Kroiss, Matthias, Zerbini, Maria Claudia Nogueira, Fragoso, Maria Candida Barisson Villares
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016635/
https://www.ncbi.nlm.nih.gov/pubmed/31963898
http://dx.doi.org/10.3390/cancers12010247
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author Lacombe, Amanda Meneses Ferreira
Soares, Iberê Cauduro
Mariani, Beatriz Marinho de Paula
Nishi, Mirian Yumie
Bezerra-Neto, João Evangelista
Charchar, Helaine da Silva
Brondani, Vania Balderrama
Tanno, Fabio
Srougi, Victor
Chambo, José Luiz
Costa de Freitas, Ricardo Miguel
Mendonca, Berenice Bilharinho
Hoff, Ana O.
Almeida, Madson Q.
Weigand, Isabel
Kroiss, Matthias
Zerbini, Maria Claudia Nogueira
Fragoso, Maria Candida Barisson Villares
author_facet Lacombe, Amanda Meneses Ferreira
Soares, Iberê Cauduro
Mariani, Beatriz Marinho de Paula
Nishi, Mirian Yumie
Bezerra-Neto, João Evangelista
Charchar, Helaine da Silva
Brondani, Vania Balderrama
Tanno, Fabio
Srougi, Victor
Chambo, José Luiz
Costa de Freitas, Ricardo Miguel
Mendonca, Berenice Bilharinho
Hoff, Ana O.
Almeida, Madson Q.
Weigand, Isabel
Kroiss, Matthias
Zerbini, Maria Claudia Nogueira
Fragoso, Maria Candida Barisson Villares
author_sort Lacombe, Amanda Meneses Ferreira
collection PubMed
description 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.
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spelling pubmed-70166352020-03-04 Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma Lacombe, Amanda Meneses Ferreira Soares, Iberê Cauduro Mariani, Beatriz Marinho de Paula Nishi, Mirian Yumie Bezerra-Neto, João Evangelista Charchar, Helaine da Silva Brondani, Vania Balderrama Tanno, Fabio Srougi, Victor Chambo, José Luiz Costa de Freitas, Ricardo Miguel Mendonca, Berenice Bilharinho Hoff, Ana O. Almeida, Madson Q. Weigand, Isabel Kroiss, Matthias Zerbini, Maria Claudia Nogueira Fragoso, Maria Candida Barisson Villares Cancers (Basel) Article 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. MDPI 2020-01-19 /pmc/articles/PMC7016635/ /pubmed/31963898 http://dx.doi.org/10.3390/cancers12010247 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lacombe, Amanda Meneses Ferreira
Soares, Iberê Cauduro
Mariani, Beatriz Marinho de Paula
Nishi, Mirian Yumie
Bezerra-Neto, João Evangelista
Charchar, Helaine da Silva
Brondani, Vania Balderrama
Tanno, Fabio
Srougi, Victor
Chambo, José Luiz
Costa de Freitas, Ricardo Miguel
Mendonca, Berenice Bilharinho
Hoff, Ana O.
Almeida, Madson Q.
Weigand, Isabel
Kroiss, Matthias
Zerbini, Maria Claudia Nogueira
Fragoso, Maria Candida Barisson Villares
Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title_full Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title_fullStr Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title_full_unstemmed Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title_short Sterol O-Acyl Transferase 1 as a Prognostic Marker of Adrenocortical Carcinoma
title_sort sterol o-acyl transferase 1 as a prognostic marker of adrenocortical carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016635/
https://www.ncbi.nlm.nih.gov/pubmed/31963898
http://dx.doi.org/10.3390/cancers12010247
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