Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2025; 31(12): 103991
Published online Mar 28, 2025. doi: 10.3748/wjg.v31.i12.103991
Increased keratin 80 expression predicts poor prognosis and promotes oxaliplatin resistance in gastric cancer
Bo Yang, Hong-Xia Cao, Ya-Wei He, Ji-Jie Ouyang, Meng Lv, Yong-Xiang Li, Yi-Da Lu
Bo Yang, Yong-Xiang Li, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Hong-Xia Cao, Department of Gastroenterology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
Ya-Wei He, Ji-Jie Ouyang, Meng Lv, Yi-Da Lu, Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
Co-first authors: Bo Yang and Hong-Xia Cao.
Co-corresponding authors: Yong-Xiang Li and Yi-Da Lu.
Author contributions: Lu YD and Yang B conceptualized and designed the research; Cao HX screened patients and acquired clinical data; He YW, Lv M and Ouyang JJ performed cell function experiments and clinical data compilation; Lu YD and Li YX wrote the paper; All authors have read and approved the manuscript. Yang B proposed, designed and performed data analysis. Cao HX was responsible for patient screening, enrollment, collection of clinical data and tissue specimens. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. Lu YD and Li YX have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors.
Supported by National Natural Science Foundation of China, No. 874063.
Institutional review board statement: The study was carried out in accordance with relevant guidelines and regulations. This present study was approved by the Institute Biomedical Research Ethics Committee of Anhui Medical University (No. YX2024-122) and written informed consent was obtained from all patients involved.
Institutional animal care and use committee statement: All experiments involving animals follow the guidelines of the Animal Center of Anhui Medical University, and all animal experimental protocols were approved by the experimental Animal Ethical Committee of Anhui Medical University, No. LLSC20180345.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Data supporting the conclusions of this article are available upon request to the corresponding author at luyida66@163.com, subject to applicable legal and ethical restrictions.
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: Yi-Da Lu, Department of General Surgery, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei 230601, Anhui Province, China. luyida66@163.com
Received: December 9, 2024
Revised: January 26, 2025
Accepted: February 24, 2025
Published online: March 28, 2025
Processing time: 110 Days and 15.7 Hours
Abstract
BACKGROUND

Keratin 80 (KRT80), a type I intermediate filament protein, is a member of the keratin family with specialized functions in epithelial tissues. While KRT80 has been implicated in both normal physiological processes and various diseases, its role in gastric cancer (GC), particularly its expression and prognostic significance, remains poorly understood. In this study, we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC. Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis. The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.

AIM

To explore the expression of KRT80 in GC and its impact on the prognosis of patients.

METHODS

KRT80 expression in GC tissues was analyzed using Western blotting, quantitative reverse transcription PCR, multiple immunofluorescence staining, and immunohistochemistry. Survival analysis was conducted using the Kaplan-Meier method with the log-rank test. The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays. Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1 (EEF1A1) as a binding protein of KRT80.

RESULTS

Integrating our experimental findings with multiple published studies, we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin. Moreover, we have preliminarily verified the interaction between KRT80 and EEF1A1. Therefore, this study provides a novel perspective on overcoming oxaliplatin resistance in GC.

CONCLUSION

Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC, suggesting its potential as a novel prognostic biomarker.

Keywords: Keratin 80; Gastric cancer; Oxaliplatin; Elongation factor 1-alpha 1; Gastrointestinal tract; Signaling pathway

Core Tip: In this paper, keratin 80 (KRT80) was found to be overexpressed in gastric cancer (GC) tissues, functioning as an oncogene and correlating with poor patient prognosis. KRT80 promoted GC proliferation, migration, invasion abilities and oxaliplatin resistance by activating the NF-κB signaling pathway. Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1 (EEF1A1) as a binding protein of KRT80, enhancing its protein stability. Notably, knockdown of EEF1A1 partially reversed the effects of KRT80 overexpression in GC cells.