Evidence map›Paper›PMID 42131723›Full record

ArticleHuman mutation2026

Convergent Immune-Coagulation Programs Underlie Gastrointestinal Bleeding Risk in Portal Vein Tumor Thrombosis-Associated Hepatocellular Carcinoma and Portal Hypertension.

Xu Rutao, Xiong Zhuxiang, Zhao Jichun, Zheng Tinghui, Zhang Kewei, Wang Qingqing, Yuan Ding, Chen Xiyang, Weng Chengxin, Huang Bin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human mutation, 2026. 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

10 authors.

Xu RutaoDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.ORCID https://orcid.org/0000-0001-7863-9187
Xiong ZhuxiangDepartment of Cardiac and Macrovascular Surgery, Nanchong Hospital of Beijing Anzhen Hospital, Capital Medical University, Nanchong, China, ccmu.edu.cn.
Zhao JichunDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.
Zheng TinghuiDepartment of Mechanics and Engineering, College of Architecture & Environment, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.ORCID https://orcid.org/0000-0002-0597-3245
Zhang KeweiDepartment of Vascular Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China, zzu.edu.cn.
Wang QingqingDepartment of Vascular Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, China, zzu.edu.cn.
Yuan DingDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.
Chen XiyangDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.
Weng ChengxinDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.
Huang BinDepartment of Vascular Sugery, West China Hospital, Sichuan University, Chengdu, Sichuan, China, scu.edu.cn.ORCID https://orcid.org/0000-0003-4767-0629

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Portal vein tumor thrombosis (PVTT) and portal hypertension are major contributors to gastrointestinal bleeding in hepatocellular carcinoma (HCC), yet the molecular programs linking vascular pathology, immune dysregulation, and bleeding risk remain incompletely defined. Methods: Bulk transcriptomic datasets related to PVTT (GSE77509 and GSE69164) and noncirrhotic portal hypertension (GSE77627) were analyzed using differential expression and weighted gene coexpression network analysis to identify robust disease-associated genes. A six-gene core signature was derived by intersecting differentially expressed genes with intramodular hub genes across datasets. Bleeding risk-associated biological programs, including coagulation, complement activation, angiogenesis, hypoxia, and inflammatory signaling, were quantified using ssGSEA. Immune infiltration was estimated using CIBERSORTx. Single-cell RNA-sequencing data from PVTT (GSE149614) were analyzed to resolve cell type-specific expression patterns and intercellular communication. Associations with survival, DNA methylation, immune infiltration, drug sensitivity, and molecular interactions were evaluated using public cancer genomics resources. Functional validation was performed using siRNA-mediated knockdown and drug treatment assays in HepG2 and Huh7 cells, followed by proliferation, colony formation, and wound healing assays. Results: Bleeding risk-related biological programs exhibited dataset-specific activation patterns and correlated with expression of the six-gene signature. Single-cell analysis revealed heterogeneous, cell type-specific expression across malignant, stromal, endothelial, and immune populations. OGFRL1 and WDR62 were significantly associated with overall survival and showed methylation-linked transcriptional regulation. Genetic silencing or pharmacological targeting of these genes significantly suppressed HCC cell proliferation, clonogenicity, and migration in vitro. Drug signature analysis and molecular docking supported potential interactions of nocodazole with OGFRL1 and testosterone with WDR62, which phenocopied knockdown effects. Conclusion: These findings identify immune-coagulation dysregulation as a molecular link between PVTT, portal hypertension, and gastrointestinal bleeding risk in HCC and functionally validate OGFRL1 and WDR62 as biologically and therapeutically relevant targets.

Indexed as

Blood CoagulationCarcinoma, HepatocellularHypertension, PortalLiver NeoplasmsPortal VeinVenous ThrombosisGene Expression ProfilingGene Expression Regulation, NeoplasticHumansTranscriptomegastrointestinal bleeding riskhepatocellular carcinomaimmune–coagulation dysregulationportal hypertensionportal vein tumor thrombosis

Identifiers

PMID42131723
PMCPMC13162123

What OpenQuestion holds

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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 OpenQuestion graph.