Titre
Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.
Type
article
Institution
Externe
Périodique
Auteur(s)
Malouf, G.G.
Auteure/Auteur
Job, S.
Auteure/Auteur
Paradis, V.
Auteure/Auteur
Fabre, M.
Auteure/Auteur
Brugières, L.
Auteure/Auteur
Saintigny, P.
Auteure/Auteur
Vescovo, L.
Auteure/Auteur
Belghiti, J.
Auteure/Auteur
Branchereau, S.
Auteure/Auteur
Faivre, S.
Auteure/Auteur
de Reyniès, A.
Auteure/Auteur
Raymond, E.
Auteure/Auteur
Liens vers les personnes
ISSN
1527-3350
Statut éditorial
Publié
Date de publication
2014
Volume
59
Numéro
6
Première page
2228
Dernière page/numéro d’article
2237
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov' tPublication Status: ppublish
Résumé
Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of liver cancer occurring mostly in children and young adults. We have shown that FLC comprises two separate entities: pure (p-FLC) and mixed-FLC (m-FLC), differing in clinical presentation and course. We show that p-FLCs have a distinct gene expression signature different from that of m-FLCs, which have a signature similar to that of classical hepatocellular carcinomas. We found p-FLC profiles to be unique among 263 profiles related to diverse tumoral and nontumoral liver samples. We identified two distinct molecular subgroups of p-FLCs with different outcomes. Pathway analysis of p-FLCs revealed ERBB2 overexpression and an up-regulation of glycolysis, possibly leading to compensatory mitochondrial hyperplasia and oncocytic differentiation. Four of the sixteen genes most significantly overexpressed in p-FLCs were neuroendocrine genes: prohormone convertase 1 (PCSK1); neurotensin; delta/notch-like EGF repeat containing; and calcitonin. PCSK1 overexpression was validated by immunohistochemistry, yielding specific, diffuse staining of the protein throughout the cytoplasm, possibly corresponding to a functional form of this convertase.
CONCLUSION: p-FLCs have a unique transcriptomic signature characterized by the strong expression of specific neuroendocrine genes, suggesting that these tumors may have a cellular origin different from that of HCC. Our data have implications for the use of genomic profiling for diagnosis and selection of targeted therapies in patients with p-FLC.
CONCLUSION: p-FLCs have a unique transcriptomic signature characterized by the strong expression of specific neuroendocrine genes, suggesting that these tumors may have a cellular origin different from that of HCC. Our data have implications for the use of genomic profiling for diagnosis and selection of targeted therapies in patients with p-FLC.
Sujets
PID Serval
serval:BIB_4B30DF4AA0A3
PMID
Open Access
Oui
Date de création
2015-02-11T11:11:13.614Z
Date de création dans IRIS
2025-05-20T13:37:18Z