Evidence map›Paper›PMID 40775116›Full record

ArticleDiscover oncology2025

Mendelian randomization analysis of inflammatory biomarkers and hepatocellular carcinoma risk: genetic causality and single-cell transcriptomics.

GuangXin Shao, Xiao Yun, Hongyue Xie, Beicheng Sun

Abstract read
In one paragraph

Article in Discover oncology, 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

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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

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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. Review
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

4 authors.

GuangXin ShaoDepartment of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu Province, China.
Xiao YunDepartment of Hepatopancreatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, P.R. China.
Hongyue XieDepartment of Hepatobiliary Surgery, Graduate School of Peking Union Medical College, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China.
Beicheng SunDepartment of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, Jiangsu Province, China. sunbc@ahmu.edu.cn.

Funding

Clinical Research Special Project of Anhui Provincial Department of Science and Technology 202204295107020008National Natural Science Foundation 82120108012 and 81930086Research Program of Anhui Provincial Department of Education 2022AH010070
6 · The paper itself

Abstract

backgroundThe causal relationship between inflammatory biomarkers and hepatocellular carcinoma (HCC) risk remains unclear. This study aimed to investigate the causal associations between various inflammation-related biomarkers and HCC risk using Mendelian randomization (MR) analysis, complemented by single-cell transcriptomic validation.

methodsWe conducted comprehensive MR analyses using multiple statistical approaches including MR Egger, weighted median, inverse variance weighted, weighted mode, and simple mode methods to evaluate causal relationships between inflammatory biomarkers and HCC risk. Over 20-30 single nucleotide polymorphisms (SNPs) were employed as instrumental variables for each biomarker. Single-cell RNA sequencing data from four HCC samples (BT1306, BT1307, scrSOL004, scrSOL006) were analyzed to validate findings through cellular heterogeneity analysis, cell-cell communication networks, and pathway enrichment analysis.

resultsMR analysis identified differential causal effects of inflammatory biomarkers on HCC risk. Protective factors included CCL7 (OR: 0.524-0.714), CCL11 (OR: 0.660-0.752), IFN-gamma (OR: 0.657), NT-3 (OR: 0.520), and TWEAK_TNFSF12 (OR: 0.804), suggesting these factors may reduce HCC risk through immune modulation. Conversely, risk factors comprised CASP-8 (OR: 1.530), CD5 (OR: 2.079), FGF-21 (OR: 2.052), and CCL2 (OR: 2.440), with CCL2 showing the strongest pathogenic association. Single-cell analysis successfully identified 29 distinct cell subpopulations and revealed complex intercellular communication networks involving MIF, MK, and ncWNT signaling pathways. CCL2 and CCL8 demonstrated significant positive correlation (r = 0.4362, p < 0.001) across multiple cell types, with fibroblasts and malignant cells serving as central communication hubs.

conclusionsThis study provides robust genetic evidence for causal relationships between specific inflammatory biomarkers and HCC risk through MR analysis.

Indexed as

Hepatocellular carcinomaInflammatory biomarkersMendelian randomizationSingle-cell transcriptomics

Identifiers

PMID40775116
PMCPMC12331562

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.