Evidence map›Paper›PMID 29774579›Full record

ArticleHepatology (Baltimore, Md.)2018

Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma.

Minmin Liu, Lian Zhang, Hongtao Li, Toshinori Hinoue, Wanding Zhou, Hitoshi Ohtani, Anthony El-Khoueiry, John Daniels, Casey O'Connell, Tanya B Dorff and 3 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 64 citations in OpenAlex.

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  5. Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 2 countries.

Minmin LiuDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Lian ZhangDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Hongtao LiDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Toshinori HinoueVan Andel Research Institute, Grand Rapids, MI.
Wanding ZhouVan Andel Research Institute, Grand Rapids, MI.
Hitoshi OhtaniDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Anthony El-KhoueiryDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
John DanielsDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Casey O'ConnellDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Tanya B DorffDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.ORCID 0000-0001-5990-298X
Qianjin LuDepartment of Dermatology, Hunan Key Laboratory of Medical Epigenomics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Daniel J WeisenbergerDepartment of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Gangning LiangDepartment of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA.
University of Southern California · USVan Andel Institute · USCentral South University · CN

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
Targeting DNA Methylation and the Cancer EpigenomeR35CA209859 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI PETER A JONES · 2017 to 2026
$11.9M
NCI NIH HHS P30 CA014089NCI NIH HHS R35 CA209859
6 · The paper itself

Abstract

There is an urgent need to develop more effective therapies for hepatocellular carcinoma (HCC) because of its aggressiveness. Guadecitabine (SGI-110) is a second-generation DNA methyltransferase inhibitor (DNMTi), which is currently in clinical trials for HCC and shows greater stability and performance over first-generation DNMTis. In order to identify potential therapeutic targets of SGI-110 for clinical trials, HCC cell lines (SNU398, HepG2, and SNU475) were used to evaluate the effects of transient SGI-110 treatment by an integrative analysis of DNA methylation, nucleosome accessibility, gene expression profiles, and its clinical relevance by comparison to The Cancer Genome Atlas (TCGA) HCC clinical data. Each HCC cell line represents a different DNA methylation subtype of primary HCC tumors based on TCGA data. After SGI-110 treatment, all cell lines were sensitive to SGI-110 with prolonged antiproliferation effects. Expression of up-regulated genes, including tumor suppressors, was positively correlated with nucleosome accessibility and negatively correlated with gene promoter DNA methylation. Alternatively, expression of down-regulated genes, such as oncogenes, was negatively correlated with nucleosome accessibility and positively correlated with gene body DNA methylation. SGI-110 can also act as a dual inhibitor to down-regulate polycomb repressive complex 2 (PRC2) genes by demethylating their gene bodies, resulting in reactivation of PRC2 repressed genes without involvement of DNA methylation. Furthermore, it can up-regulate endogenous retroviruses to reactivate immune pathways. Finally, about 48% of frequently altered genes in primary HCC tumors can be reversed by SGI-110 treatment.

conclusionOur integrative analysis has successfully linked the antitumor effects of SGI-110 to detailed epigenetic alterations in HCC cells, identified potential therapeutic targets, and provided a rationale for combination treatments of SGI-110 with immune checkpoint therapies.

Indexed as

Gene Expression Regulation, NeoplasticAzacitidineCarcinoma, HepatocellularCell Line, TumorDNA MethylationEnzyme InhibitorsEpigenomicsHumansLiver NeoplasmsMethyltransferasesMolecular Targeted TherapySensitivity and SpecificityAzacitidineEnzyme InhibitorsguadecitabineMethyltransferases

Identifiers

PMID29774579
PMCPMC6173644
OpenAlexW2803869134

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.