Expression of C19MC miRNAs in HCC associates with stem-cell features and the cancer-testis genes signature

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)583-593
JournalDigestive and Liver Disease
Volume50
Issue number6
DOIs
Publication statusPublished - 2018

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Neoplasm Genes
Testicular Neoplasms
MicroRNAs
Hepatocellular Carcinoma
Stem Cells
Atlases
Population
Antigens
Immunotherapy
Genome
Chromosomes, Human, Pair 19
Neoplasms
Disease Resistance
Neoplastic Stem Cells
Immunohistochemistry
Recurrence
Proteins

Keywords

  • C19MC miRNAs
  • CT antigens
  • HCC
  • Side Population

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

@article{0510aed45a304fc58e3686a29010dad8,
title = "Expression of C19MC miRNAs in HCC associates with stem-cell features and the cancer-testis genes signature",
abstract = "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.",
keywords = "C19MC miRNAs, CT antigens, HCC, Side Population",
author = "Claudia Augello and Federico Colombo and Andrea Terrasi and Elena Trombetta and Marco Maggioni and Laura Porretti and Giorgio Rossi and Silvana Guerneri and Rosamaria Silipigni and Silvano Bosari and Valentina Vaira",
year = "2018",
doi = "10.1016/j.dld.2018.03.026",
language = "English",
volume = "50",
pages = "583--593",
journal = "Digestive and Liver Disease",
issn = "1590-8658",
publisher = "Elsevier B.V.",
number = "6",

}

TY - JOUR

T1 - Expression of C19MC miRNAs in HCC associates with stem-cell features and the cancer-testis genes signature

AU - Augello, Claudia

AU - Colombo, Federico

AU - Terrasi, Andrea

AU - Trombetta, Elena

AU - Maggioni, Marco

AU - Porretti, Laura

AU - Rossi, Giorgio

AU - Guerneri, Silvana

AU - Silipigni, Rosamaria

AU - Bosari, Silvano

AU - Vaira, Valentina

PY - 2018

Y1 - 2018

N2 - 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.

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.

KW - C19MC miRNAs

KW - CT antigens

KW - HCC

KW - Side Population

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