Evidence map›Paper›PMID 40038575›Full record

ArticleBiomarker research2025

Folate receptor 1 is a stemness trait-associated diagnostic and prognostic marker for hepatocellular carcinoma.

Yuto Shiode, Takahiro Kodama, Yu Sato, Ryo Takahashi, Takayuki Matsumae, Kumiko Shirai, Akira Doi, Yuki Tahata, Hayato Hikita, Tomohide Tatsumi and 5 more

Abstract read
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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

15 authors.

Yuto Shiode *Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Takahiro Kodama *Department of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Yu SatoDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Ryo TakahashiDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Takayuki MatsumaeDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Kumiko ShiraiDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Akira DoiDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Yuki TahataDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Hayato HikitaDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Tomohide TatsumiDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan.
Moto FukaiDepartment of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Akinobu TaketomiDepartment of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Mathuros RuchirawatLaboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, 10210, Thailand.
Xin Wei WangLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Tetsuo TakeharaDepartment of Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, 2-2 Yamadaoka Suita, Osaka, 565-0871, Japan. takehara@gh.med.osaka-u.ac.jp.

Funding

The identification of human hepatocellular carcinoma metastasis genesZIABC010877 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WANG, XIN WEI · 2009 to 2025
$8.3M
CCR NIH HHS ZIABC010877Intramural NIH HHS ZIA BC010877Japan Agency for Medical Research and Development JP24fk0210131Japan Society for the Promotion of Science 23H02893
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) can be classified into several subtypes based on molecular traits, aiding in prognostic stratification. The subtype with a poor prognosis is often associated with stem/progenitor features. This study focused on identifying circulating biomarkers for aggressive HCC.

methodsWe searched for secretory proteins whose expression was positively associated with the stem/progenitor markers KRT19, EPCAM, and PROM1 in 2 independent HCC cohorts. Serum folate receptor 1 (FOLR1) levels were measured in 238 chronic liver disease and 247 HCC patients, evaluating their diagnostic and prognostic capabilities.

resultsFOLR1 was identified as a secretory protein that was positively correlated with all 3 stem/progenitor markers and a poor prognosis in both the discovery and validation cohorts. Higher FOLR1 expression was detected in tumor than nontumor tissues and was associated with aggressive subtypes, and activation of p53, DNA repair, Myc, E2F, and PI3K/AKT/mTOR pathways. Serum FOLR1 levels correlated with tumoral FOLR1 expression in HCC patients and were significantly elevated compared with those in patients with chronic hepatitis or nonliver disease. Serum FOLR1 levels demonstrated diagnostic performance for HCC comparable to that of alpha-fetoprotein (AFP), and their combination increased the diagnostic accuracy. Elevated serum FOLR1 levels were associated with poor prognosis in HCC patients, regardless of treatment, especially in patients with early-stage disease. The multivariate analysis revealed that the serum FOLR1 level and the Gender, Age, AFP-L3, AFP, and Des-gamma-carboxy prothrombin (GALAD) score were independent predictors of a poor prognosis with their combination further stratifying prognosis.

conclusionsFOLR1 is a stemness-associated biomarker for HCC, with serum levels serving as a diagnostic marker for HCC and a prognostic indicator for early-stage disease.

Indexed as

BiomarkerDiagnosisFOLR1HCCPrognosis

Identifiers

PMID40038575
PMCPMC11877696

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.