Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs.
Methods: Clinical and specimen data from 130 adrenocortical carcinoma (ACC) patients was acquired from the Cancer Genome Atlas (TCGA) database (n = 79) and a West China Hospital (WCH) cohort (n = 51). In the WCH cohort, archived formalin-fixed paraffin embedded (FFPE) samples were collected for immunohistochemical analysis. The correlation between the EMT genes and the tumour microenvironment status was estimated based on the Tumour Immune Estimation Resource (TIMER) algorithm. Kaplan-Meier analysis, followed by univariate and multivariate regression analyses, were performed to identify the prognostic association of FSCN1 and FOXM1.
Results: FSCN1 and FOXM1 were over-expressed in ACC tissue when compared with adrenocortical adenoma and normal adrenal tissue. Over-expression of FSCN1 or FOXM1 was associated with the tumour microenvironment and immune signatures in ACCs. Patients with higher expression of FSCN1 or FOXM1 were more likely to have worse prognoses. The prognostic effects were further verified in both early (stage I/II) and advanced (stage III/IV) ACCs. Furthermore, FSCN1 and FOXM1 appeared as independent prognostic factors in ACC.
Conclusions: These results show that FSCN1 and FOXM1 are independent prognostic factors in ACCs and over-expression of FSCN1 or FOXM1 indicates a worse prognosis.
Keywords: Adrenocortical carcinoma; EMT; FOXM1; FSCN1; Prognosis.