Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours

• Published in: Investigational new drugs Vol. 38; no. 3; pp. 899 - 908
• Main Authors: dos Santos Passaia, Bárbara, Lima, Keli, Kremer, Jean Lucas, da Conceição, Barbara Brito, de Paula Mariani, Beatriz Marinho, da Silva, Jean Carlos Lipreri, Zerbini, Maria Claudia Nogueira, Fragoso, Maria Candida Barisson Villares, Machado-Neto, João Agostinho, Lotfi, Claudimara Ferini Pacicco
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2020; Springer Nature B.V
• Subjects: Adenoma; Biotechnology; Cancer; Cell adhesion & migration; Cell culture; Cell migration; Clinical trials; Gene expression; Malignancy; Medicine; Medicine & Public Health; mRNA; Neuroendocrine tumors; Oncology; Paclitaxel; Pediatrics; Pharmacology/Toxicology; Phenotypes; PTEN-induced putative kinase; Short Report; Stathmin; Survival; Tumors; Adrenocortical adenoma; Adrenocortical carcinoma; STMN1; Paclitaxel; Stathmin 1
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-019-00846-9

Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study, STMN1 mRNA levels were significantly higher ( p  < 0.05) in ACC patients, especially in an advanced stage, and correlated with BUB1B and PINK1 expression, the prognostic-related genes in ACC. In paediatric tumours, high STMN1 expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours, STMN1 level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08, p  = 0.002; disease-free survival: hazard ratio = 4.65, p  < 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all p  < 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.