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

• Published in: Cancers Vol. 12; no. 1; p. 247
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.01.2020; MDPI
• Subjects: Biomarkers; Cancer; Cell viability; Cholesterol; Esterification; Gene expression; Homeostasis; Immunohistochemistry; Lipids; Malignancy; Medical prognosis; Metabolism; Metastasis; Multivariate analysis; Patients; Polymerase chain reaction; Prognosis; Protein expression; Proteins; Steroidogenesis; Sterols; Survival analysis; Tumorigenesis; Tumors; adrenocortical carcinoma; prognostic factors; target therapies; SOAT1
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12010247

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 ( = 0.01), an advanced disease stage [European Network for the Study of Adrenal Tumors (ENSAT) staging system 3 and 4 ( = 0.011)] and a high Ki67 index ( = 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; = 0.005) in all patients ( = 112), and a reduced RFS (HR 2.1, CI 95% 1.09-4.06; = 0.027) in patients with localized disease at diagnosis ( = 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.