EIF5B/mitogen-activated protein kinase 1 axis drives tumor progression and confers dual resistance to chemotherapy and immunotherapy in colonic adenocarcinoma

doi:10.3748/wjg.121829

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Nov 21, 2026; 32(43): 121829
Published online Nov 21, 2026. doi: 10.3748/wjg.121829

EIF5B/mitogen-activated protein kinase 1 axis drives tumor progression and confers dual resistance to chemotherapy and immunotherapy in colonic adenocarcinoma

Wen-Xu Li, Qi-Zhong Shi, Yong-Hui Mu, Cheng-Lei Li, Suliman Khan, Wen-Chao Zhao, Na Han

Wen-Xu Li, Na Han, Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, Henan Province, China

Qi-Zhong Shi, Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, Henan Province, China

Yong-Hui Mu, General Practice School, Xinxiang Medical University, Xinxiang 453003, Henan Province, China

Cheng-Lei Li, Wen-Chao Zhao, Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China

Suliman Khan, Medical Research Center, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, Henan Province, China

Co-corresponding authors: Wen-Chao Zhao and Na Han.

Author contributions: Zhao WC and Han N contributed to the conception and design of the study and supervised all work; Li WX wrote the first draft of the manuscript, conducted cell-based experiments, and performed the statistical analyses; Zhao WC and Khan S revised the initial draft; Zhao WC, Han N, Li CL, and Li WX analyzed the bioinformatical data; Shi QZ, Mu YH, and Han N provided colonic adenocarcinoma samples and detected eukaryotic translation initiation factor 5B expression; All authors read and approved the final manuscript. We propose the designation of two co-corresponding authors to formally acknowledge their shared, equal responsibility for the scientific integrity, methodological rigor, and long-term reproducibility of this fully experimental study.

AI contribution statement: AI tools were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.

Supported by Henan Provincial Natural Science Foundation, No. 252300421368; Top Talents Funding of the Second Affiliated Hospital of Zhengzhou University, No. 2020BJRCB04; and Beijing Science and Technology Innovation Medical Development Foundation, No. KC2023-JX-0186-FM054.

Institutional review board statement: The study was reviewed and approved by the Second Affiliated Hospital of Zhengzhou University Institutional Review Board (Approval No. KY2025211).

Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Second Affiliated Hospital of Zhengzhou University (IACUC protocol number: No. KY2025211).

Conflict-of-interest statement: The have no conflicts of interest to declare.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets generated and/or analyzed during this study will be made available by the corresponding author upon reasonable request.

Corresponding author: Na Han, MD, Chief Physician, Department of Oncology, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Road, Jinshui District, Zhengzhou 450014, Henan Province, China. hannahappy@zzu.edu.cn

Received: April 7, 2026
Revised: May 8, 2026
Accepted: June 25, 2026
Published online: November 21, 2026
Processing time: 176 Days and 4.5 Hours

Abstract

BACKGROUND

Although eukaryotic translation initiation factor 5B (EIF5B) is implicated in the pathogenesis of multiple malignancies, its functional impact in colonic adenocarcinoma (COAD) is still not well defined.

AIM

To determine EIF5B’s role, mechanisms, and therapeutic associations in COAD.

METHODS

To assess the prognostic value of EIF5B, we integrated pan-cancer bioinformatic screening with clinical validation in COAD cohorts. The oncogenic function and molecular regulations were evaluated through in vitro and in vivo assays, multi-omic pathway enrichment, Western blotting, rescue experiments, immune infiltration and drug-sensitivity modeling.

RESULTS

Our results showed significant overexpression of EIF5B in COAD tissues, and its correlation with unfavorable patient outcomes. Functional analysis revealed that EIF5B induced migration, proliferation, and invasion in vitro, as well as promoted tumorigenesis in vivo through phosphorylation of mitogen-activated protein kinase 1 (MAPK1). In addition, the immune microenvironment exhibited a suppressed phenotype, accompanied by decreased predictive scores for programmed cell death protein 1/cytotoxic T lymphocyte-associated antigen-4 blockade and reduced predicted sensitivity to chemotherapeutic agents. EIF5B expression, immune evasion, and drug sensitivity were associated with the MAPK signaling pathway.

CONCLUSION

EIF5B mediated phosphorylation of MAPK1 regulates the progression of COAD, suggesting EIF5B as potential therapeutic target for overcoming resistance against chemotherapy and immunotherapy.

Keywords: Colonic adenocarcinoma; Eukaryotic translation initiation factor 5B; Mitogen-activated protein kinase 1; Proliferation; Immune infiltration; Drug sensitivity

Core Tip: This study identified eukaryotic translation initiation factor 5B (EIF5B) as a novel oncogenic driver in colonic adenocarcinoma. EIF5B was upregulated in tumor tissues and associated with poor prognosis. Functional experiments showed that EIF5B promoted tumor cell proliferation, migration, invasion, and xenograft growth by enhancing mitogen-activated protein kinase 1 phosphorylation. High EIF5B expression was also linked to an immunosuppressive tumor microenvironment, lower predicted responses to programmed cell death protein 1/cytotoxic T lymphocyte-associated antigen-4 blockade, and reduced sensitivity to standard chemotherapeutic agents. EIF5B may serve as both a prognostic biomarker and therapeutic target for overcoming chemotherapy and immunotherapy resistance in colonic adenocarcinoma.