Fascin-1 Is a Novel Prognostic Biomarker Associated With Tumor Invasiveness in Adrenocortical Carcinoma

Abstract

Context Novel tumor markers are urgently needed to better stratify adrenocortical cancer (ACC) patients and improve therapies for this aggressive neoplasm. Objective To assess the diagnostic and prognostic value of the actin-bundling protein fascin-1 (FSCN1) in adrenocortical tumors. Design, Setting and Participants A local series of 37 malignant/37 benign adrenocortical tumors at Careggi University Hospital and two independent validation ACC cohorts (Cochin, TCGA) from the European Network for the Study of Adrenal Tumors were studied. Main Outcome Measures FSCN1 expression was quantified by immunohistochemistry, Western blot and quantitative RT-PCR in ACC specimens; overall and disease-free survival associated with FSCN1 expression were assessed by Kaplan-Meier analysis and compared with that of Ki67 labeling index and tumor stage. Results Despite the low diagnostic power, in the Florence ACC series, FSCN1 immunohistochemical detection appeared as an independent prognostic factor, also refining results obtained with staging and Ki67 labeling index. The robust prognostic power of FSCN1 levels was further confirmed in two independent ACC cohorts. A positive correlation was found between FSCN1 and steroidogenic factor-1 (SF-1), with a substantially higher expression of both factors in ACCs at advanced stages and with at least one of the three Weiss score parameters associated with invasiveness. Moreover, we demonstrated FSCN1 role in promoting cell invasion in a human ACC cell line only in the case of increased SF-1 dosage. Conclusions These findings show that FSCN1 is a novel independent prognostic marker in ACC and may serve as a potential therapeutic target to block tumor spread.

The Adipose Stem Cell as a Novel Metabolic Actor in Adrenocortical Carcinoma Progression: Evidence from an In Vitro Tumor Microenvironment Crosstalk Model

“…Consistently, we found a significant increase in the expression of IL-8 in ASCs when co-cultured with H295R cells, suggesting that the IL-8 production may contribute to leptin promotion of the aggressive phenotype in H295R cells. In addition, we observed an increased protein expression of Fascin-1, an actin-binding protein participating in the organization and functionality of cell protrusions, recently shown to associate with ACC invasiveness [46].…”

“…Tumor stage was evaluated according to the revised TNM classification of ACC proposed by the European Network for the Study of Adrenal Tumors [58]. The Weiss score parameter of capsular invasion was reported in this study from our cohort of patients with ACC stage 3-4 (n = 15, stage 3 and n = 4, stage 4) [46,59].…”

Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma

“…To overcome this limitation, we retrieved external quantitative data from the TCGA cohort in this study, successfully validating the prognostic effects of CD276. The clinical pathological characteristics of the validation cohort were summarized in a previous report [34]. Clinically, multiple parameters have [35][36][37][38][39][40].…”

FSCN1 is an effective marker of poor prognosis and a potential therapeutic target in human tongue squamous cell carcinoma

“…The FSCN1 gene was expressed much higher in TSCC tissues than in normal tongue tissues. As the up-regulation of Fascin protein expression has been confirmed in many cancers, such as esophagus carcinoma 7 , non-small cell lung cancer 8 , breast cancer 9 , gastric carcinoma 10 , pancreatic ductal adenocarcinoma 11 , ovarian cancer 12 , and adrenocortical carcinoma 13 , we hypothesized that FSCN1 might be a biomarker in TSCC. We then verify our hypothesis by studying TSCC cell viability and trans-migration in vitro, tumor growth in vivo and FSCN1 expression and patient survival analysis.…”

“…Recent studies have shown that Fascin plays a critical role in cell migration, motility, adhesion, and cellular interactions 5,6 . The up-regulation of Fascin protein expression has been found in many cancers, such as esophageal carcinoma 7 , non-small cell lung cancer 8 , breast cancer 9 , gastric carcinoma 10 , pancreatic ductal adenocarcinoma 11 , ovarian cancer 12 , and adrenocortical carcinoma 13 , thus we hypothesized that Fascin might play a vital role in the malignant transformation of squamous cell epithelium 14 . To evaluate the relationship between the expression of Fascin protein and TSCC, we explored the expression and function of FSCN1 in TSCC cells in vitro and in vivo.…”