Jing LB, Liu J, Yang ZH, Yang FF, Wang DG, Li YM. Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications. World J Gastrointest Oncol 2026; 18(2): 114351 [DOI: 10.4251/wjgo.v18.i2.114351]
Corresponding Author of This Article
Yu-Min Li, MD, PhD, Chief Physician, Professor, The Second Hospital and Clinical Medical School, Lanzhou University, No. 82 Cuiying Gate, Lanzhou 730000, Gansu Province, China. liym@lzu.edu.cn
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Gastroenterology & Hepatology
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Review
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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/
Feb 15, 2026 (publication date) through Feb 3, 2026
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World Journal of Gastrointestinal Oncology
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1948-5204
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Jing LB, Liu J, Yang ZH, Yang FF, Wang DG, Li YM. Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications. World J Gastrointest Oncol 2026; 18(2): 114351 [DOI: 10.4251/wjgo.v18.i2.114351]
World J Gastrointest Oncol. Feb 15, 2026; 18(2): 114351 Published online Feb 15, 2026. doi: 10.4251/wjgo.v18.i2.114351
Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications
Li-Baihe Jing, Jie Liu, Zi-Hai Yang, Fei-Fei Yang, De-Gui Wang, Yu-Min Li
Li-Baihe Jing, Gansu Provincial Key Laboratory of Environmental Oncology, The Second Hospital and Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China
Jie Liu, Zi-Hai Yang, Fei-Fei Yang, The Second Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
De-Gui Wang, Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu Province, China
Yu-Min Li, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
Co-corresponding authors: De-Gui Wang and Yu-Min Li.
Author contributions: Jing LB participated in manuscript editing; Jing LB and Liu J contributed to the literature search; Jing LB and Li YM participated in the quality assessment; Yang ZH participated in figure generation and manuscript writing; Yang FF contributed to data collection; Wang DG and Li YM were responsible for review conception, protocol design, supervision, and review of the manuscript as co-corresponding authors; all of the authors read and approved the final version of the manuscript to be published.
Supported by Chief Scientist Project of Gansu Province, No. 22JR9KA002; Project of Gansu Provincial Department of Education, No. 2021jyjbgs-02; Key Research and Development Program of Gansu Province, No. 20ZD7FA003; National Natural Science Foundation of Gansu Province, No. 25JRRA582; Project of Basic Scientific Research Business Expenses of Central Universities, No. 561225004; and Second Hospital of Lanzhou University Internal Talent Recruitment Program Fund, No. yjrckyqdj-2024-02.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu-Min Li, MD, PhD, Chief Physician, Professor, The Second Hospital and Clinical Medical School, Lanzhou University, No. 82 Cuiying Gate, Lanzhou 730000, Gansu Province, China. liym@lzu.edu.cn
Received: September 17, 2025 Revised: November 3, 2025 Accepted: December 2, 2025 Published online: February 15, 2026 Processing time: 139 Days and 14.7 Hours
Abstract
Gastric cancer (GC) remains among the leading causes of cancer-related mortality globally. Increasing evidence indicates that metallic elements such as iron, copper (Cu2+), zinc, and calcium (Ca2+) play crucial roles in GC pathogenesis, diagnosis, and treatment through diverse molecular mechanisms. This review systematically summarizes recent advances in the application of metallomics in GC. Relevant studies published up to 2024 were retrieved from PubMed, Web of Science, and Scopus using keywords including “gastric cancer”, “metal ions”, “metallomics”, and “metal-based therapy”. After screening and evaluation, representative studies elucidating the roles of metallic elements in GC were analyzed and synthesized. The findings revealed that iron overload induces oxidative stress and immune suppression via the Fenton reaction. Further analysis indicated that Cu2+ imbalance triggers mitochondrial dysfunction and cuproptosis, zinc deficiency disrupts transcriptional regulation through zinc finger proteins and metalloproteinases, and Ca2+ dysregulation activates Ca2+/calmodulin-dependent protein kinase kinase- AMP-activated protein kinase signaling to promote proliferation and chemoresistance. Advances in analytical techniques such as laser ablation inductively coupled plasma mass spectrometry have enabled spatial mapping of metal distributions in tumors, providing novel diagnostic and prognostic insights. Moreover, metal-based anti-cancer drugs and combination regimens involving traditional Chinese medicines exhibit promising therapeutic potential. Understanding the molecular crosstalk of metal metabolism offers new perspectives for precision diagnosis and targeted treatment in GC.
Core Tip: Metallomics, a study of metallic elements in biological systems, is critical for understanding gastric cancer (GC). It helps identify biomarkers for early diagnosis and offers insights into treatment strategies. Novel biomarkers like matrix metalloproteinases, ferritin, and zinc (Zn2+) finger proteins can improve the sensitivity and accuracy of GC diagnosis compared to conventional tumor markers. Role of metals in GC: (1) Iron: Altered iron metabolism is linked to GC progression and can serve as a prognostic marker; (2) Copper: Copper imbalances contribute to GC development, and supplementation may enhance therapeutic effects; (3) Zn2+: Zn2+ stability is essential for cell function, and imbalances may indicate GC risk; and (4) Calcium: Abnormal calcium signal transduction may promote the occurrence, migration, invasion and other aspects of GC and affect prognosis. Metallomics faces challenges in identifying and quantifying metal-related biomarkers, dealing with low concentrations of elements, and overcoming issues with drug resistance. Advancements in analytical techniques and combining metal-based drugs with traditional therapies could improve GC diagnosis and treatment outcomes.
