EPHA3, upregulated in high-risk histological subtypes of gastrointestinal stromal tumor, promotes GIST progression

Han Wei; Jia Zhao; Hongmei Wang; Lihong Guo; Yanhong Liu; Chuntao Wang; Liang Yang; Zhi Qi; Wencong Tian; Lei Cao; Yang Gao

doi:10.2478/raon-2026-0042

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EPHA3, upregulated in high-risk histological subtypes of gastrointestinal stromal tumor, promotes GIST progression

Radiology and Oncology

Volume 60 (2026): Issue 3 (September 2026)

By: Han Wei, Jia Zhao, Hongmei Wang, Lihong Guo, Yanhong Liu, Chuntao Wang, Liang Yang, Zhi Qi, Wencong Tian, Lei Cao and Yang Gao

Open Access

|Sep 2026

Abstract

Background

To explore the expression pattern and functional role of EPH receptor A3 (EPHA3) in high-risk gastrointestinal stromal tumors (GISTs) and its potential relevance to tumor progression.

Materials and methods

Immunohistochemical (IHC) analysis was performed to evaluate EPHA3 expression across a pilot cohort of clinical GIST specimens with different risk stratifications. The biological functions of EPHA3 in vitro were assessed using (5-ethynyl-2’-deoxyuridine, EdU) assay, colony formation, apoptosis, wound-healing, and transwell assays in EPHA3-knockout GIST-430 cells. Furthermore, RNA sequencing (RNA-seq) analysis was utilized to identify differentially expressed genes and associated signaling pathways following EPHA3 knockout.

Results

EPHA3 expression was found to be elevated in high-risk GIST specimens compared with intermediate-risk cases. Loss-of-function assays demonstrated that EPHA3 knockout attenuated cell proliferation and migration while promoting apoptosis in vitro. Pathway enrichment analysis suggested that EPHA3 expression is associated with cell adhesion, extracellular matrix interaction, and mesenchymal-related phenotypic remodeling.

Conclusions

Our findings suggest that EPHA3 is upregulated in high-risk GIST and contributes to aggressive cellular behavior in vitro. These preliminary data indicate that EPHA3 may play a role in the malignant progression of GIST, although its clinical utility as a biomarker requires further validation in larger cohorts.

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Articles in this issue

DOI: https://doi.org/10.2478/raon-2026-0042 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 416 - 426

Submitted on: May 6, 2026

Accepted on: Jun 4, 2026

Published on: Sep 7, 2026

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

EPHA3,

gastrointestinal stromal tumors (GISTs),

histological subtype,

epithelial–mesenchymal transition (EMT)

Related subjects:

Medicine,

Clinical medicine,

Radiology

© 2026 Han Wei, Jia Zhao, Hongmei Wang, Lihong Guo, Yanhong Liu, Chuntao Wang, Liang Yang, Zhi Qi, Wencong Tian, Lei Cao, Yang Gao, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 60 (2026): Issue 3 (September 2026)