Fascin-1(FSCN1) is an actin-bundling protein expressed in several solid carcinomas and often associated to an invasive and aggressive phenotype as it is involved in cytoskeleton rearrangement and filopodia formation. Adrenocortical carcinoma (ACC) is a rare endocrine malignancy characterized by a poor prognosis, particularly when metastatic at diagnosis. Complete surgical resection of the tumor mass is the main therapy for ACC patients in addition to the adjuvant administration of mitotane. Therefore, it is necessary to identify new markers indicative of tumor progression for a better management and monitoring of the patients. In our previous work, we found that FSCN1 detected in tumor samples could represent a new prognostic biomarker for invasive ACC. The main objective of the present study was to assess if FSCN1 was also detectable in the bloodstream of ACC patients and its prognostic value. We demonstrated that FSCN1 can be detected both in serum and plasma samples of a small local cohort of ACC patients (n = 27) compared to healthy controls (n = 4), through a specific ELISA assay for human FSCN1. FSCN1 circulating levels resulted significantly higher in ACC compared to controls, (FI: 9.66±1.22, P <0.01). In addition, we longitudinally evaluated FSCN1 concentrations both in pre-operative blood samples as well after the resection of the tumor mass. Consistently, patients with stage III/IV showed levels of serum FSCN1 significantly higher than those in stage I/II both in pre- and post-surgery blood samples, (FSCN1pre: 22.8±1.1 vs 15.8±1.8 ng/ml, P <0.01; FSCN1post: 21.4±1.5 vs 18.0±0.8 ng/ml, P <0.05). In order to evaluate the prognostic power of circulating FSCN1, we performed KaplanMeier analysis of patients stratified in 2 groups of high and low FSCN1 serum levels (cut off value: median of FSCN1 distribution): the pre-operative but not the post-surgical levels of circulating FSCN1 can significantly predict tumour recurrence (Log Rank = 0.013), but nor overall survival (Log Rang = 0.317). In conclusion, these findings though preliminary suggest that circulating FSCN1 may represent a new non-invasive prognostic marker in ACC, in particular when measured before surgery and histological diagnosis.
Associazione Italiana Ricerca sul Cancro (AIRC) Investigator Grant to M.L. (#IG2015-17691); Seventh Framework Program (FP7/2007-2013) under grant agreement n° 259735 ENS@T-Cancer.
22 May 2021 - 26 May 2021