Evidence mapPaperPMID 41388436Full record

ArticleEuropean journal of medical research2025

Multimodal analysis reveals potential association of CDH13 with endothelial cells and its overexpression in hepatocellular carcinoma.

Ke-Jun Wu, Li-Hua Yang, Dong-Ming Li, Rong-Quan He, Di-Yuan Qin, Shi-De Li, Jian-Di Li, Yi-Wu Dang, Ming-Jie Li, Qi Li and 6 more

Abstract read
In one paragraph

Article in European journal of medical 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

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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. 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

16 authors.

Ke-Jun Wu *Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.ORCID http://orcid.org/0009-0007-9017-6382
Li-Hua Yang *Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Dong-Ming LiDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Rong-Quan HeDepartment of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Di-Yuan QinDepartment of Computer Science and Technology, School of Computer and Electronic Information, Guangxi University, 100 Daxuedong RD, Guangxi Zhuang Autonomous Region, Nanning, 530 004, People's Republic of China.
Shi-De LiDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Jian-Di LiDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Yi-Wu DangDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Ming-Jie LiDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Qi LiDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Jian-Jun LiDepartment of General Surgery, The Second Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
Lu ZhangDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Han HeDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Ji-Feng HeDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
Gang ChenDepartment of Pathology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China. chengang@gxmu.edu.cn.
Xiao-Bo JiangDepartment of General Practice, The First Affiliated Hospital of Guangxi Medical University, 6 Shuang yong RD, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China. jiang_xiaobo_gx@163.com.

Funding

China Undergraduate Innovation and Entrepreneurship Training Program S202310598177Future Academic Star of Guangxi Medical University WLXSZX23110Guangxi Medical University "Four New" Project SX202403Innovation Project of Guangxi Graduate Education JGY2023068National Natural Science Foundation of China NSFC82460783
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide and shows significant heterogeneity. Cadherin 13 (CDH13) is abnormally expressed in various malignancies, but its role in HCC and the tumor microenvironment remains unclear.

objectiveThis study aimed to systematically explore the expression, regulatory mechanisms, and potential functions of CDH13 in HCC using a multi-omics strategy.

methodsWe integrated transcriptomics, proteomics, spatial transcriptomics, single-cell RNA sequencing (scRNA-seq), immunohistochemistry (IHC), clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene editing, chromatin immunoprecipitation sequencing (ChIP-seq), weighted gene co-expression network analysis (WGCNA), gene set variation analysis (GSVA), immune infiltration analysis, molecular docking, phenotypic analysis, and survival analysis.

resultsIn multiple cohorts, CDH13 mRNA was significantly upregulated in 5145 HCC samples (standardized mean difference (SMD) = 1.17) and associated with poor prognosis (hazard ratio (HR) = 2.06). Protein levels were elevated in 165 public and 476 clinical paired samples (361 from Guangxi Medical University, 115 from Yulin Red Cross Hospital; SMD = 2.48), mainly localized to the cytoplasm and membrane. Spatial transcriptomics showed CDH13 enrichment in tumor regions and spatial association with endothelial cells, which was confirmed in an independent HCC tissue section. Focusing on cell function, CRISPR/Cas9 knockout of CDH13 significantly inhibited proliferation in HCC cell lines such as SNU182, SNU739, HUH7, etc. Further analysis showed CDH13 was expressed in hepatocytes, endothelial cells, and hepatitis B virus (HBV)-infected regions; pseudotime analysis indicated late-stage upregulation in endothelial cells and activation of the macrophage migration inhibitory factor (MIF) pathway. IHC confirmed moderate CDH13 positivity in tumor cells and strong positivity in microvascular endothelial cells. CDH13-high endothelial cells were enriched in pyrimidine metabolism, oxidative phosphorylation, and propanoate metabolism. WGCNA and GSVA linked CDH13-related genes to angiogenesis, invasion, and metabolic reprogramming. ChIP-seq identified binding of Forkhead box A1 (FOXA1) to CDH13 regulatory regions. Clinically, CDH13 negatively correlated with regulatory T cells (Tregs, R = -0.311) and γδ T cells (R = -0.206), and positively with stromal scores (R = 0.400). High CDH13 predicted poor immunotherapy response (Area Under the Curve (AUC) = 0.745-0.795) and prognosis. Molecular docking shows a binding with docetaxel (-7.6 kcal/mol), while phenotypic analysis showed no obvious physiological toxicity.

conclusionCDH13 is highly expressed in HCC and may promote angiogenesis, immune evasion, and metabolic reprogramming via the FOXA1-CDH13 axis, suggesting its potential as a therapeutic target.

Indexed as

CadherinsCarcinoma, HepatocellularEndothelial CellsLiver NeoplasmsBiomarkers, TumorGene Expression Regulation, NeoplasticHumansPrognosisTumor MicroenvironmentBiomarkers, TumorCadherinsH-cadherinAngiogenesisCDH13CRISPR/Cas9Endothelial cellsHepatocellular carcinoma

Identifiers

PMID41388436
PMCPMC12817644

What Socratic holds

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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.