Circulating Fascin 1 as a Promising Prognostic Marker in Adrenocortical Cancer

Abstract

Fascin-1 (FSCN1) is an actin-bundling protein associated with an invasive and aggressive phenotype of several solid carcinomas, as it is involved in cell cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by poor prognosis, particularly when metastatic at diagnosis. Radical resection is the only therapeutic option for ACC patients in addition to the adjuvant treatment with mitotane. Novel specific biomarkers suggestive of tumor progression to refine diagnosis and prognosis of patients with advanced ACC are urgently needed. ACC intratumoral FSCN1 has previously been suggested as a valid prognostic marker. In the present study, we identified FSCN1 in the bloodstream of a small cohort of ACC patients (n = 27), through a specific ELISA assay for human FSCN1. FSCN1 can be detected in the serum, and its circulating levels were evaluated in pre-surgery samples, which resulted to be significantly higher in ACC patients from stage I/II and stage III/IV compared with nontumoral healthy controls (HC, n = 4, FI: 5.5 ± 0.8, P<0.001, and 8.0 ± 0.5, P < 0.001 for stage I/II and stage III/IV group vs HC, respectively). In particular, FSCN1 levels were significantly higher in advanced stage versus stage I/II (22.8 ± 1.1 vs 15.8 ± 1.8 ng/ml, P < 0.005, respectively). Interestingly, circulating levels of pre-surgical FSCN1 can significantly predict tumor progression/recurrence (Log rank = 0.013), but not the overall survival (Log rank=0.317), in patients stratified in high/low PreS FSCN1. In conclusion, these findings—though very preliminary—suggest that circulating FSCN1 may represent a new minimally-invasive prognostic marker in advanced ACC, in particular when measured before surgery enables histological diagnosis.

FSCN1 as a new druggable target in adrenocortical carcinoma

“…FSCN1 is overexpressed in aggressive ACC, being a reliable prognostic indicator in this cancer type 19,20 . Somatic mutations of CTNNB1 , encoding β‐catenin or other genes leading to constitutive activation of the canonical Wnt pathway are present in about 1/3 of ACC, alone or in combination with other genomic alterations 38 .…”

“…FSCN1 is overexpressed in ACC compared with normal adrenal tissue 18 . Its expression levels were significantly correlated to both shortened disease‐free survival (DFS) and overall survival (OS) in three different cohorts of ACC patients 19 and high pre‐operative circulating FSCN1 levels were predictors of recurrence 20 . FSCN1 has been shown to synergize with transcription factor SF‐1 and the Rho/Rac guanine nucleotide exchange factor (GEF) VAV2 21 in enhancing the invasion properties of ACC cancer cells 19 .…”

“…18 Its expression levels were significantly correlated to both shortened disease-free survival (DFS) and overall survival (OS) in three different cohorts of ACC patients 19 and high pre-operative circulating FSCN1 levels were predictors of recurrence. 20 FSCN1 has been shown to synergize with transcription factor SF-1 and the Rho/Rac guanine nucleotide exchange factor (GEF) VAV2 21 in enhancing the invasion properties of ACC cancer cells. 19 Based on those results, we investigated the effects of FSCN1 inactivation by CRISPR/Cas9 or pharmacological blockade on the invasive properties of ACC cells, both in vitro and in an in vivo metastatic ACC model in zebrafish.…”

The level of fascin-1 in circulating tumor cells and in cells of the local tumor site in patients with head and neck squamous cell carcinoma

“…[37; 38]. The cut-off values for FSCN1 in patients with non-small cell lung cancer (NSCLC) was reported to be 4.35 ng/mL, and tissue and serum FSCN1 levels were associated with relapse in NSCLC patients [39]. According to the literature data, the cut-off values for FSCN1 in blood serum of healthy controls have not been determined yet [40].…”

The prognostic value and immunological role of SULF2 in adrenocortical carcinoma

“…Even so, unfortunately, most patients who have undergone radical surgery still develop local recurrence and metastasis [ 2 ]. With regard to the prognostic factors of ACC, in addition to tumor stage, the reference value of gene sequencing and other molecular biological examinations is limited although they have been available [ 3 , 4 ].…”