PMID- 29673952
OWN - NLM
STAT- MEDLINE
DCOM- 20181026
LR  - 20220409
IS  - 1878-3562 (Electronic)
IS  - 1590-8658 (Linking)
VI  - 50
IP  - 6
DP  - 2018 Jun
TI  - Expression of C19MC miRNAs in HCC associates with stem-cell features and the 
      cancer-testis genes signature.
PG  - 583-593
LID - S1590-8658(18)30667-4 [pii]
LID - 10.1016/j.dld.2018.03.026 [doi]
AB  - BACKGROUND: Intratumor heterogeneity of hepatocellular carcinoma (HCC) and, among 
      HCC cell subsets, the cancer stem cell population (hCSC), is responsible for 
      therapeutic resistance and disease relapse. AIMS: To characterize hCSC-enriched 
      HCCs at the molecular level. METHODS: Side population (SP) was used to identify 
      the hCSCs in multiple tumor sampling from different patients and primary HCCs 
      cultures. FACS was used to immunoprofile cultures. miRNAs were profiled in 
      samples and correlated to SP. The Cancer Genome Atlas (TCGA) HCC dataset was 
      analyzed to search for signatures associated with C19MC miRNAs expression. 
      Results were confirmed by immunohistochemistry. RESULTS: The miRNA cluster on 
      chromosome 19 (C19MC) was enriched in SP and in HCCs with a high SP fraction. At 
      the molecular level, an elevated C19MC was correlated with expression of 
      precursor transcripts. In TCGA-HCC series, high C19MC expression identified a 
      subset of patients with poorer prognosis, advanced disease and overexpression of 
      the cancer-testis (CT) antigens. These data were confirmed in an independent 
      cohort of HCCs and at the protein level. CONCLUSION: C19MC miRNAs and CT antigens 
      overexpression represents a novel oncogenic pathway in a subset of hCSC-enriched 
      HCCs with dismal prognosis. CT antigens are promising immunotherapy targets. 
      Therefore, these molecular signatures could identify HCCs who could benefit from 
      immunotherapy.
CI  - Copyright (c) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Augello, Claudia
AU  - Augello C
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy; Divisions of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Colombo, Federico
AU  - Colombo F
AD  - Clinical Chemistry and Microbiology Laboratory, Flow Cytometry and Experimental 
      Hepatology Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      Milan, Italy.
FAU - Terrasi, Andrea
AU  - Terrasi A
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy; Divisions of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Trombetta, Elena
AU  - Trombetta E
AD  - Clinical Chemistry and Microbiology Laboratory, Flow Cytometry and Experimental 
      Hepatology Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      Milan, Italy.
FAU - Maggioni, Marco
AU  - Maggioni M
AD  - Divisions of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Porretti, Laura
AU  - Porretti L
AD  - Clinical Chemistry and Microbiology Laboratory, Flow Cytometry and Experimental 
      Hepatology Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 
      Milan, Italy.
FAU - Rossi, Giorgio
AU  - Rossi G
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy; General Surgery and Liver Transplantation, Fondazione IRCCS Ca' Granda 
      Ospedale Maggiore Policlinico, Milan, Italy.
FAU - Guerneri, Silvana
AU  - Guerneri S
AD  - Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Silipigni, Rosamaria
AU  - Silipigni R
AD  - Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy.
FAU - Bosari, Silvano
AU  - Bosari S
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy; Divisions of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy. Electronic address: silvano.bosari@unimi.it.
FAU - Vaira, Valentina
AU  - Vaira V
AD  - Department of Pathophysiology and Transplantation, University of Milan, Milan, 
      Italy; Divisions of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore 
      Policlinico, Milan, Italy. Electronic address: valentina.vaira@unimi.it.
LA  - eng
PT  - Journal Article
DEP - 20180330
PL  - Netherlands
TA  - Dig Liver Dis
JT  - Digestive and liver disease : official journal of the Italian Society of 
      Gastroenterology and the Italian Association for the Study of the Liver
JID - 100958385
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/genetics
MH  - Carcinogenesis/genetics
MH  - Carcinoma, Hepatocellular/*pathology
MH  - Chromosomes, Human, Pair 19/*genetics
MH  - Cohort Studies
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Liver Neoplasms/*pathology
MH  - Male
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - MicroRNAs/*genetics
MH  - Neoplasm Transplantation
MH  - Neoplastic Stem Cells/*cytology
MH  - Side-Population Cells/cytology
OTO - NOTNLM
OT  - C19MC miRNAs
OT  - CT antigens
OT  - HCC
OT  - Side Population
EDAT- 2018/04/21 06:00
MHDA- 2018/10/27 06:00
CRDT- 2018/04/21 06:00
PHST- 2017/07/11 00:00 [received]
PHST- 2018/03/20 00:00 [revised]
PHST- 2018/03/22 00:00 [accepted]
PHST- 2018/04/21 06:00 [pubmed]
PHST- 2018/10/27 06:00 [medline]
PHST- 2018/04/21 06:00 [entrez]
AID - S1590-8658(18)30667-4 [pii]
AID - 10.1016/j.dld.2018.03.026 [doi]
PST - ppublish
SO  - Dig Liver Dis. 2018 Jun;50(6):583-593. doi: 10.1016/j.dld.2018.03.026. Epub 2018 
      Mar 30.