Evidence map›Paper›PMID 40993762›Full record

ArticleBiomarker research2025

Long non-coding RNA PWRN4 associated with post-SVR hepatocellular carcinoma: a genome-wide association study.

Goki Suda, Masaya Sugiyama, Hayato Hikita, Akira Nishio, Tomohide Tatsumi, Tetsuo Takehara, Miyako Murakawa, Mina Nakagawa, Yasuhiro Asahina, Masashi Mizokami and 23 more

Abstract readLetter
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors.

Goki Suda *Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan. gsudgast@pop.med.hokudai.ac.jp.
Masaya Sugiyama *Department of Viral Pathogenesis and Controls, National Institute of Global Health and Medicine, Japan Institute for Health Security, Ichikawa, Japan.
Hayato HikitaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Akira NishioDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Tomohide TatsumiDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Tetsuo TakeharaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Miyako MurakawaDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Mina NakagawaDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Yasuhiro AsahinaDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Masashi MizokamiCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Tatsuhiko KakisakaDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Yuzuru SakamotoDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Akinobu TaketomiDepartment of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Koji MiyanishiDepartment of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yoshiyuki UenoDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Hiroaki HagaDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Shinya MaekawaGastroenterology and Hepatology Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Nobuyuki EnomotoGastroenterology and Hepatology Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Masayuki KurosakiDepartment of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
Motoyuki KohjimaDepartment of Gastroenterology, NHO Kyushu Medical Center, Fukuoka, Japan.
Makoto NakamutaDepartment of Gastroenterology, NHO Kyushu Medical Center, Fukuoka, Japan.
Yasuhito TanakaDepartment of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yoshiya YamamotoDepartment of Gastroenterology and Hepatology, Hakodate Municipal Hospital, Hakodate, Hakodate, Japan.
Masaru BabaCenter for Gastroenterology and Hepatology, Japan Community Healthcare Organization Hokkaido Hospital, Sapporo, Japan.
Hisatoshi HanamatsuInstitute for Glyco-Core Research (iGCORE), Nagoya University, Nagoya, Japan.
Jun-Ichi FurukawaInstitute for Glyco-Core Research (iGCORE), Nagoya University, Nagoya, Japan.
Masatsugu OharaDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Takashi KitagatayaDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Naoki KawagishiDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Masato NakaiDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Takuya ShoDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Koji OgawaDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan.
Naoya SakamotoDepartment of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Hokkaido, Japan. sakamoto@med.hokudai.ac.jp.

Funding

Japan Agency for Medical Research and Development,Japan JP25fk0210126, JP25fk0310545, JP24fk0210121, JP25fk0210142, JP25fk0310551, JP25fk0210123, JP25fk0310535, JP25fk0210157, JP25fk0310543, JP25fk0210172 JP25fk0210174, JP25fk0210143.
6 · The paper itself

Abstract

A subset of patients still develops hepatocellular carcinoma (HCC) even after eradication of the hepatitis-C virus (HCV) by anti-HCV treatment. We conducted a genome-wide association study (GWAS) to identify host genetic factors associated with HCC development following HCV eradication in Japan. In this GWAS (n = 517), the discovery cohort included 118 patients without HCC and 67 who developed HCC following HCV eradication with interferon-based therapy. A genome-wide scan for HCC-associated variants was conducted. An independent cohort of 274 patients without HCC and 58 patients with post-eradication HCC was used for replication. The effects of candidate gene variants were assessed clinically and through in vitro cellular assays. The GWAS identified significant variants associated with HCC development following HCV eradication, including rs4778350, located near the long non-coding RNA Prader-Willi non-protein coding RNA 4 (PWRN4) on chromosome 15. In the combined analysis, rs4778350 remained significantly associated with HCC, showing a high odds ratio of 5.86 (95% CI, 3.63-9.44). The frequency of the A allele in rs4778350 differs across ethnic populations. Multivariate analysis revealed that female sex, high platelet count, and higher serum albumin levels were associated with reduced HCC risk, while fibrosis stage F4 and the AA genotype of rs4778350 were linked to increased risk. The AA genotype of rs4778350 enhanced PWRN4 expression, promoting cell proliferation, migration, and invasion. These findings suggest a role for PWRN4 in hepatocarcinogenesis through its association with rs4778350 in patients achieving HCV eradication.

Indexed as

Genome-wide association studyHepatitis cHepatocellular carcinomaLong non-coding RNASingle nucleotide polymorphism

Identifiers

PMID40993762
PMCPMC12462314

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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.