Cargando…
Comprehensive molecular and immunological characterization of hepatocellular carcinoma
BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with various etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multi-focal recurrence. We herein identified three major subtypes of HCC by performing integrative analysis of tw...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412165/ https://www.ncbi.nlm.nih.gov/pubmed/30598371 http://dx.doi.org/10.1016/j.ebiom.2018.12.058 |
_version_ | 1783402542296727552 |
---|---|
author | Shimada, Shu Mogushi, Kaoru Akiyama, Yoshimitsu Furuyama, Takaki Watanabe, Shuichi Ogura, Toshiro Ogawa, Kosuke Ono, Hiroaki Mitsunori, Yusuke Ban, Daisuke Kudo, Atsushi Arii, Shigeki Tanabe, Minoru Wands, Jack R. Tanaka, Shinji |
author_facet | Shimada, Shu Mogushi, Kaoru Akiyama, Yoshimitsu Furuyama, Takaki Watanabe, Shuichi Ogura, Toshiro Ogawa, Kosuke Ono, Hiroaki Mitsunori, Yusuke Ban, Daisuke Kudo, Atsushi Arii, Shigeki Tanabe, Minoru Wands, Jack R. Tanaka, Shinji |
author_sort | Shimada, Shu |
collection | PubMed |
description | BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with various etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multi-focal recurrence. We herein identified three major subtypes of HCC by performing integrative analysis of two omics data sets, and clarified that this classification was closely correlated with clinicopathological factors, immune profiles and recurrence patterns. METHODS: In the test study, 183 tumor specimens surgically resected from HCC patients were collected for unsupervised clustering analysis of gene expression signatures and comparative analysis of gene mutations. These results were validated by using genome, methylome and transcriptome data of 373 HCC patients provided from the Cancer Genome Atlas Network. In addition, omics data were obtained from pairs of primary and recurrent HCC. FINDINGS: Comprehensive molecular evaluation of HCC by multi-platform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying immune suppression; and (3) metabolic disease-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly distinguished between HCC with intrahepatic metastasis (IM) and multi-centric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not correlated to the IM/MC origin, but to the classification. Interpretation: Identification of these HCC subtypes provides further insights into patient stratification as well as presents opportunities for therapeutic development. FUND: Ministry of Education, Culture, Sports, Science and Technology of Japan (16H02670 and 18K19575), Japan Agency for Medical Research and Development (JP15cm0106064, JP17cm0106518, JP18cm0106540 and JP18fk0210040). |
format | Online Article Text |
id | pubmed-6412165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-64121652019-03-21 Comprehensive molecular and immunological characterization of hepatocellular carcinoma Shimada, Shu Mogushi, Kaoru Akiyama, Yoshimitsu Furuyama, Takaki Watanabe, Shuichi Ogura, Toshiro Ogawa, Kosuke Ono, Hiroaki Mitsunori, Yusuke Ban, Daisuke Kudo, Atsushi Arii, Shigeki Tanabe, Minoru Wands, Jack R. Tanaka, Shinji EBioMedicine Research paper BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous disease with various etiological factors, and ranks as the second leading cause of cancer-related mortality worldwide due to multi-focal recurrence. We herein identified three major subtypes of HCC by performing integrative analysis of two omics data sets, and clarified that this classification was closely correlated with clinicopathological factors, immune profiles and recurrence patterns. METHODS: In the test study, 183 tumor specimens surgically resected from HCC patients were collected for unsupervised clustering analysis of gene expression signatures and comparative analysis of gene mutations. These results were validated by using genome, methylome and transcriptome data of 373 HCC patients provided from the Cancer Genome Atlas Network. In addition, omics data were obtained from pairs of primary and recurrent HCC. FINDINGS: Comprehensive molecular evaluation of HCC by multi-platform analysis defined three major subtypes: (1) mitogenic and stem cell-like tumors with chromosomal instability; (2) CTNNB1-mutated tumors displaying immune suppression; and (3) metabolic disease-associated tumors, which included an immunogenic subgroup characterized by macrophage infiltration and favorable prognosis. Although genomic and epigenomic analysis explicitly distinguished between HCC with intrahepatic metastasis (IM) and multi-centric HCC (MC), the phenotypic similarity between the primary and recurrent tumors was not correlated to the IM/MC origin, but to the classification. Interpretation: Identification of these HCC subtypes provides further insights into patient stratification as well as presents opportunities for therapeutic development. FUND: Ministry of Education, Culture, Sports, Science and Technology of Japan (16H02670 and 18K19575), Japan Agency for Medical Research and Development (JP15cm0106064, JP17cm0106518, JP18cm0106540 and JP18fk0210040). Elsevier 2018-12-29 /pmc/articles/PMC6412165/ /pubmed/30598371 http://dx.doi.org/10.1016/j.ebiom.2018.12.058 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Shimada, Shu Mogushi, Kaoru Akiyama, Yoshimitsu Furuyama, Takaki Watanabe, Shuichi Ogura, Toshiro Ogawa, Kosuke Ono, Hiroaki Mitsunori, Yusuke Ban, Daisuke Kudo, Atsushi Arii, Shigeki Tanabe, Minoru Wands, Jack R. Tanaka, Shinji Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title | Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title_full | Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title_fullStr | Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title_full_unstemmed | Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title_short | Comprehensive molecular and immunological characterization of hepatocellular carcinoma |
title_sort | comprehensive molecular and immunological characterization of hepatocellular carcinoma |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412165/ https://www.ncbi.nlm.nih.gov/pubmed/30598371 http://dx.doi.org/10.1016/j.ebiom.2018.12.058 |
work_keys_str_mv | AT shimadashu comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT mogushikaoru comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT akiyamayoshimitsu comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT furuyamatakaki comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT watanabeshuichi comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT oguratoshiro comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT ogawakosuke comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT onohiroaki comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT mitsunoriyusuke comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT bandaisuke comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT kudoatsushi comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT ariishigeki comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT tanabeminoru comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT wandsjackr comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma AT tanakashinji comprehensivemolecularandimmunologicalcharacterizationofhepatocellularcarcinoma |