Evidence map›Paper›PMID 40245183›Full record

ArticleJournal of cellular and molecular medicine2025

Crosstalk Between Gastric Cancer and Adjacent Mucosa Reveals EDN1-EDNRA-Mediated Regulation of Cancer Stemness and Immunomodulation Networks.

Xiaobin Zhu, Yating Zhang, Hanlin Liao, Jing Hu, Xiao Xiao

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 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

5 authors.

Xiaobin ZhuDepartment of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, People's Republic of China.ORCID 0000-0001-5516-9215
Yating ZhangInstitute of Health Inspection and Testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei, People's Republic of China.
Hanlin LiaoDepartment of Medical Services Section, Taihe Hospital, Hubei University of Medicine, Shiyan, People's Republic of China.
Jing HuOccupational Disease Prevention and Control Department, Center for Disease Control and Prevention of Yangtze River Navigation Administration, Wuhan, Hubei, People's Republic of China.
Xiao XiaoDepartment of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.ORCID 0000-0001-9738-7157

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Within the complex system of gastric cancer, the tumour microenvironment mediates a complex network of cellular interactions, yet its tissue-specific intracellular communication patterns have remained poorly understood. Leveraging cutting-edge single-cell RNA sequencing, we investigated two independent research studies (GSE183904 and GSE184198), creating an unprecedented map of cellular crosstalk across gastric cancer tissues, their adjacent normal tissue and gastric mucosa (GM). Our systematic analysis revealed two distinct patterns: 7557 distinct interactions from normal tissue to tumour cells, while gastric mucosa engaged in 7320 unique interactions with malignant conditions. Within this cellular network, the endothelin pathway emerged as a key regulator, specifically increased in gastric mucosa-to-tumour interaction. The Cancer Genome Atlas data demonstrated that patients harbouring elevated EDNRA expression faced significantly poorer outcomes. EDNRA, previously underexplored in this context, showed remarkable upregulation across diverse gastric cancer cell lines. Through experimental validation, we demonstrated that EDNRA overexpression, when stimulated by endothelin-1, dramatically accelerated the proliferation of human gastric epithelial GSE-1 cells. Conversely, pharmacological inhibition of EDNRA using ABT-627 suppressed both NCI-N87 and MKN-28 gastric cancer cells proliferation. Further mechanistic investigation revealed the molecular mechanism of ABT-627: simultaneously triggering both extrinsic and intrinsic apoptotic cascades. TISIDB analysis revealed significant positive correlations between EDNRA and multiple immunostimulators, suggesting the role of EDNRA in immunomodulation networks. These findings reveal a previously unidentified connection between gastric mucosa and tumour progression, positioning EDNRA not only as a molecular target, but also as a critical mediator of tissue-specific cancer communication. In conclusion, EDNRA functions as both a regulatory factor and therapeutic target, offering a promising therapeutic avenue for gastric cancer intervention.

Indexed as

Endothelin-1Gastric MucosaImmunomodulationNeoplastic Stem CellsReceptor, Endothelin AStomach NeoplasmsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansSignal TransductionTumor MicroenvironmentEndothelin-1Receptor, Endothelin Aapoptosiscell–cell communicationendothelin receptor agastric cancerimmunomodulationsingle‐cell RNA sequencingtumour microenvironment

Identifiers

PMID40245183
PMCPMC12005395

What Socratic 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 Socratic graph.