FSCN1 and epithelial mesenchymal transformation transcription factor expression in human pancreatic intraepithelial neoplasia and ductal adenocarcinoma

Morris, H. T. , Bamlet, W. R., Razidlo, G. L. and Machesky, L. M. (2023) FSCN1 and epithelial mesenchymal transformation transcription factor expression in human pancreatic intraepithelial neoplasia and ductal adenocarcinoma. Pathology: Research and Practice, 251, 154836. (doi: 10.1016/j.prp.2023.154836) (PMID:37832352) (PMCID:37832352)

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Background: The actin regulatory protein fascin (FSCN1) and epithelial mesenchymal transition (EMT) transcription factor (TF) SLUG/SNAI2 have been shown to be expressed in PDAC and its precursor lesions (pancreatic intraepithelial neoplasia (PanIN), graded 1-3) in in vitro and murine in vivo studies. Our aim was to investigate the expression of FSCN1 and EMT-TFs and their association with survival in human PanIN and PDAC. Methods: Expression was investigated in silico using TCGA PanCancer Atlas data (177 PDAC samples with mRNA data) and immunohistochemical staining of a tissue microarray (TMA) (59 PDAC patients). Results: High FSCN1 expression was associated with poorer overall survival (p = 0.02) in the TCGA data. EMT-TF expression was not associated with survival, however FSCN1 expression correlated with that of the EMT-TFs SLUG/SNAI2 (rho = 0.49, p<0.001) and TWIST1 (rho = 0.52, p<0.001). TMA IHC showed low expression of SNAI2 and TWIST1 in normal ductal epithelium, while FSCN1 was not expressed. SNAI2 increased slightly in PanIN1-2, then decreased in higher grade lesions. TWIST1 increased in PanIN2-3 and was retained in PDAC. FSCN1 was increasingly expressed from PanIN2 onwards. SNAI2 and TWIST1 expression positively correlated in all grades of PanIN and PDAC (rho = 0.52, p<0.001). FSCN1 correlated positively with SNAI2 in PanIN1 (rho = 0.56, p<0.01). Conclusions: Increased expression of EMT-TFs in low-grade PanIN followed by FSCN1 in PanIN3 and PDAC suggests EMT-TFs may trigger FSCN1 expression and are potential early diagnostic markers. FSCN1 expression correlated with overall survival in PDAC and may have value as a prognostic marker.

Item Type:Articles
Additional Information:This study was supported in part by the Mayo Clinic SPORE in Pancreatic Cancer (NCI grant P50 CA102701), CRUK core funding to the CRUK Beatson Institute (A31287) and CRUK core funding to LMM (A24452 and DRCQQR-Jun22\100003).
Glasgow Author(s) Enlighten ID:Machesky, Professor Laura and Morris, Dr Hayley
Creator Roles:
Morris, H.Conceptualization, Methodology, Formal analysis, Writing – original draft, Writing – review and editing
Machesky, L.Conceptualization, Methodology, Supervision, Writing – review and editing
Authors: Morris, H. T., Bamlet, W. R., Razidlo, G. L., and Machesky, L. M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Pathology: Research and Practice
ISSN (Online):1618-0631
Published Online:02 October 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Pathology: Research and Practice 251:154836
Publisher Policy:Reproduced under a Creative Commons License

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