Clinical and Translational Research
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Abstract
BACKGROUND

Breast cancer (BC) remains a public health problem. Tamoxifen (TAM) resistance has caused great difficulties for treatment of BC patients. Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and progression of BC. However, the expression and mechanism of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients are still unclear.

AIM

To investigate the expression and functions of EIF4EBP1 in determining the efficacy of TAM therapy in BC patients.

METHODS

High-throughput sequencing data of breast tumors were downloaded from the Gene Expression Omnibus database. Differential gene expression analysis identified EIF4EBP1 to be significantly upregulated in cancer tissues. Its prognostic value was analyzed. The biological function and related pathways of EIF4EBP1 was analyzed. Subsequently, the expression of EIF4EBP1 was determined by real-time reverse transcription polymerase chain reaction and western blotting. Cell Counting Kit-8 assays, colony formation assay and wound healing assay were used to understand the phenotypes of function of EIF4EBP1.

RESULTS

EIF4EBP1 was upregulated in the TAM-resistant cells, and EIF4EBP1 was related to the prognosis of BC patients. Gene Set Enrichment Analysis showed that EIF4EBP1 might be involved in Hedgehog signaling pathways. Decreasing the expression of EIF4EBP1 could reverse TAM resistance, whereas overexpression of EIF4EBP1 promoted TAM resistance.

CONCLUSION

This study indicated that EIF4EBP1 was overexpressed in the BC and TAM-resistant cell line, which increased cell proliferation, invasion, migration and TAM resistance in BC cells.

Keywords: Breast cancer, Eukaryotic translation initiation factor 4E binding protein 1, Tamoxifen, Resistance, Prognosis, Bioinformatics

Core Tip: Breast cancer is the most frequently diagnosed cancer in women and the leading cause of female deaths from cancer worldwide. Eukaryotic translation initiation factor 4E binding protein 1 was overexpressed in the breast cancer tamoxifen-resistant cell line, and high expression of eukaryotic translation initiation factor 4E binding protein 1 was associated with poor prognosis in tamoxifen-treated patients.