Yan YJ, Yang Z, Chao RY, Shi JL. E74-like E26 transformation-specific transcription factor 3 in gastric cancer: Functions, mechanisms, and clinical translation - unresolved issues. World J Gastrointest Oncol 2026; 18(8): 120240 [DOI: 10.4251/wjgo.v18.i8.120240]
Corresponding Author of This Article
Yun-Jun Yan, PhD, Jinan Vocational College of Nursing, No. 3636 Gangxi Road, Licheng District, Jinan 250102, Shandong Province, China. yanyunjunou@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Aug 15, 2026; 18(8): 120240 Published online Aug 15, 2026. doi: 10.4251/wjgo.v18.i8.120240
E74-like E26 transformation-specific transcription factor 3 in gastric cancer: Functions, mechanisms, and clinical translation - unresolved issues
Jun-Li Shi, Ruo-Yu Chao, Zhen Yang, Yun-Jun Yan
Yun-Jun Yan, Zhen Yang, Ruo-Yu Chao, Jun-Li Shi, Jinan Vocational College of Nursing, Jinan 250102, Shandong Province, China
Co-first authors: Yun-Jun Yan and Zhen Yang.
Author contributions: Yan YJ and Yang Z contributed equally to this work as co-first authors. Yan YJ and Yang Z designed the overall concept and outline of the manuscript; Chao RY and Shi JL contributed to the literature review and analysis; Yan YJ and Yang Z wrote and edited the manuscript; and all authors reviewed and approved the final version.
AI contribution statement: AI tools (DeepSeek) were used for initial Chinese-to-English translation of the manuscript. The translated text was then professionally edited for language by Medjaden. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All authors take full responsibility for the accuracy, originality, and integrity of this manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Received: February 24, 2026 Revised: March 26, 2026 Accepted: May 7, 2026 Published online: August 15, 2026 Processing time: 164 Days and 12.7 Hours
Abstract
Gastric cancer is one of the most common malignancies worldwide, with gastric adenocarcinoma accounting for more than 90% of all cases. Despite the advances in treatment, the prognosis for patients with advanced disease remains extremely poor, highlighting the urgent need for novel biomarkers and therapeutic targets. E26 transformation-specific (ETS) transcription factor E74-like ETS transcription factor 3 (ELF3) exhibits context-dependent regulatory functions in epithelial-derived malignancies, acting either as an oncogene or a tumor suppressor, depending on the cellular context. A recent study on gastric cancer was the first to systematically delineate the expression profile and clinical significance of ELF3, proposing a dual mechanism that may contribute to tumor progression. In the broader context of ELF3 research, the present opinion review focused on three core issues: (1) Is the function of ELF3 consistent between gastric cancer and other tumors; (2) To what extent does present evidence support the dual-action model of ELF3 in regulating CDH1 and CXCL11; and (3) What are the clinical translational prospects of ELF3 as both a biomarker and a therapeutic target? By systematically reviewing the available evidence and identifying key research gaps, the present study aims to provide a clear analytical framework for future investigations, ultimately translating ELF3 biology into clinical practice.
Core Tip: E74-like E26 transformation-specific transcription factor 3 (ELF3) exhibits context-dependent functions in gastric cancer. Present evidence supports its pro-tumorigenic role through the regulation of epithelial-mesenchymal transition and immune evasion, although functional validation remains required. Patients with high ELF3 expression present with a “cold” tumor phenotype that may limit the responsiveness to immunotherapy. Future research should focus on completing the chain of functional validation and systematically evaluating existing ELF3-targeting compounds in gastric cancer models, particularly in combination with immune checkpoint inhibitors.
