Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.
Details
Serval ID
serval:BIB_4B30DF4AA0A3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Transcriptional profiling of pure fibrolamellar hepatocellular carcinoma reveals an endocrine signature.
Journal
Hepatology
ISSN
1527-3350 (Electronic)
ISSN-L
0270-9139
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
59
Number
6
Pages
2228-2237
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov' tPublication Status: ppublish
Abstract
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.
Keywords
Adult, Calcitonin/genetics, Calcitonin/metabolism, Carcinoma, Hepatocellular/metabolism, Female, Gene Expression Profiling, Genes, erbB-2, Glycolysis/genetics, Humans, Liver Neoplasms/metabolism, Male, Nerve Tissue Proteins/genetics, Nerve Tissue Proteins/metabolism, Neurotensin/genetics, Neurotensin/metabolism, Proprotein Convertase 1/genetics, Proprotein Convertase 1/metabolism, Receptor, ErbB-2/metabolism, Receptors, Cell Surface/genetics, Receptors, Cell Surface/metabolism, Transcription, Genetic
Pubmed
Open Access
Yes
Create date
11/02/2015 13:11
Last modification date
20/08/2019 14:59