Yang S, Hui TL, Wang HQ, Zhang X, Mi YZ, Cheng M, Gao W, Geng CZ, Li SN. High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer. World J Clin Cases 2023; 11(20): 4788-4799 [PMID: 37583983 DOI: 10.12998/wjcc.v11.i20.4788]
Corresponding Author of This Article
Sai-Nan Li, Doctor, Surgeon, Department of Breast Center, The Fourth Hospital of Hebei Medical University, No. 169 Tianshan Street, Shijiazhuang 050011, Hebei Province, China. lisainan01@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
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 Clin Cases. Jul 16, 2023; 11(20): 4788-4799 Published online Jul 16, 2023. doi: 10.12998/wjcc.v11.i20.4788
High expression of autophagy-related gene EIF4EBP1 could promote tamoxifen resistance and predict poor prognosis in breast cancer
Shan Yang, Tian-Li Hui, Hao-Qi Wang, Xi Zhang, Yun-Zhe Mi, Meng Cheng, Wei Gao, Cui-Zhi Geng, Sai-Nan Li
Shan Yang, Tian-Li Hui, Hao-Qi Wang, Xi Zhang, Yun-Zhe Mi, Meng Cheng, Wei Gao, Cui-Zhi Geng, Sai-Nan Li, Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Author contributions: Li SN and Yang S contributed to conception, design and writing of the manuscript; Hui TL, Mi YZ, Zhang X and Wang HQ performed the research; Cheng M, Gao W, Geng CZ and Li SN contributed to analysis and interpretation of data; and all authors read and approved the final manuscript.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (Approval No. 2022KY396).
Clinical trial registration statement: Human tissues were used for immunohistochemistry and real-time reverse transcription polymerase chain reaction to observe the expression of EIF4EBP1. All participants signed informed consent, but it did not interfere with the normal treatment activities of participants. Therefore, it does not belong to the scope of clinical trial registration, and the approval of clinical trial registration cannot be provided.
Informed consent statement: Informed consent was obtained from all patients at the time of sample collection.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at lisainan01@163.com.
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: Sai-Nan Li, Doctor, Surgeon, Department of Breast Center, The Fourth Hospital of Hebei Medical University, No. 169 Tianshan Street, Shijiazhuang 050011, Hebei Province, China. lisainan01@163.com
Received: March 20, 2023 Peer-review started: March 20, 2023 First decision: April 11, 2023 Revised: April 24, 2023 Accepted: June 13, 2023 Article in press: June 13, 2023 Published online: July 16, 2023 Processing time: 113 Days and 17.4 Hours
ARTICLE HIGHLIGHTS
Research background
Tamoxifen (TAM) resistance is a major obstacle in the treatment of breast cancer (BC) patients. It has been reported that eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and development of BC.
Research motivation
TAM resistance remains one of the major causes of BC mortality today. Therefore, it is necessary to identify biomarkers and therapeutic targets and understand molecular mechanisms of TAM resistance to help patients.
Research objectives
The objective was to investigate the expression and functions of EIF4EBP1 in the efficacy of TAM therapy in BC patients.
Research methods
Gene Set Enrichment Analysis (GSEA) was performed to explore the biological functions and related pathways of EIF4EBP1. Real-time reverse transcription polymerase chain reaction were employed to explore the expression of EIF4EBP1 in TAM-resistant and TAM-sensitive BC cell lines. Cell count kit-8 assay, colony formation experiments and the wound healing assay were used to understand the phenotypes of loss- and gain-of-function of EIF4EBP1 in a TAM-resistant cell line.
Research results
EIF4EBP1 was upregulated in TAM resistant cells, and EIF4EBP1 was associated with the prognosis of BC patients. GSEA suggested that EIF4EBP1 may be involved in the Hedgehog signaling pathway. Reducing the expression of EIF4EBP1 can reverse TAM resistance, while overexpression of EIF4EBP2 can promote TAM resistance.
Research conclusions
In this study, we investigated the role of EIF4EBP1 in TAM resistance. Scholars have performed studies on the role of EIF4EBP1 in TAM resistance, and their conclusions of these studies were similar with no controversy. However, most of these conclusions were based on bioinformatics analysis. The role of EIF4EBP1 in TAM resistance has not been experimentally demonstrated. This study indicated that EIF4EBP1 enhanced the resistance of T47D-R cells to TAM. In addition, our GSEA results may provide new insights into the molecular mechanism of TAM resistance. In brief, EIF4EBP1 could be a marker for the early diagnosis and a therapeutic target for the therapy of TAM resistance.
Research perspectives
Further studies should explore the potential function and molecular mechanism of EIF4EBP1 in TAM-resistant BC cells through in vitro and in vivo experiments.
