PMID- 38312639
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240206
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 10
IP  - 2
DP  - 2024 Jan 30
TI  - A bioinformatic analysis found low expression and clinical significance of ATF4 
      in breast cancer.
PG  - e24669
LID - 10.1016/j.heliyon.2024.e24669 [doi]
LID - e24669
AB  - BACKGROUND: Activating Transcription Factor 4 (ATF4) expression exhibits 
      differential patterns across different types of tumors. Besides, the pathogenesis 
      of breast cancer is complex, and the exact relationship between ATF4 and ATF4 
      remains uncertain. METHODS: The analysis of ATF4 expression was conducted by 
      utilizing The Cancer Genome Atlas (TCGA) pan-cancer data, while the gene 
      expression profile of breast cancer was checked by the comprehensive 
      database-Gene Expression Omnibus database. In order to gain a more comprehensive 
      understanding of the specific cell types that exhibit ATF4 expression within the 
      microenvironment of breast cancer, we conducted a single-cell analysis of ATF4 
      using two distinct datasets of human breast cancer (GSE114717 and GSE11088, 
      respectively). The spatial distribution of ATF4 within a tissue was demonstrated 
      based on datasets obtained from the Human Protein Atlas (HPA) and SpatialDB. The 
      clinical prognostic significance of ATF4 was assessed by analyzing clinical 
      survival data obtained from TCGA, GSE4830, and GSE25055 datasets. We used the R 
      package clusterProfiler to carry out an enrichment analysis of ATF4. We assessed 
      how ATF4 impacts the growth and movement of breast cancer cell lines. We 
      manipulated ATF4 levels using plasmid transfection techniques. RESULTS: The 
      expression of ATF4 was found to be suboptimal and demonstrated a significant 
      correlation with enhanced disease-specific survival (p = 0.012) and overall 
      survival (p = 0.032) in breast cancer as well as other malignancies. We conducted 
      an analysis to investigate the interaction between the infiltration level of 
      immune cells and the expression of ATF4, using samples obtained from TCGA with 
      known immune cell infiltration scores. Furthermore, a notable positive 
      correlation exists between the elevated expression of ATF4 and immune-related 
      genomes, specifically those associated with chemokine as well as immunity. 
      Subsequent examination revealed a notable augmentation in the cytodifferentiation 
      of T cells into regulatory T (Treg) cells within tissues exhibiting elevated 
      levels of ATF4 expression. ATF4 exhibits notable upregulation in the 
      MDA-MB-231 cell, thereby exerting a substantial impact on cell proliferation and 
      migration upon its knockdown. Conversely, the overexpression of ATF4 in the MCF7 
      Luminal A breast cancer cell line can also modulate cellular function. 
      CONCLUSIONS: Our study suggests that ATF4 helps T cells differentiate into Treg 
      cells in breast cancer. ATF4 can represent a clinically useful biomarker to 
      predict the overall survival rate, especially in patients with different subtypes 
      of breast cancer. Provide certain guidance value for the development of targeted 
      drugs or inhibitors targeting ATF4.
CI  - (c) 2024 The Authors.
FAU - Shao, Lujing
AU  - Shao L
AD  - Department of Oncology, East Hospital Affiliated to Tongji University, Tongji 
      University School of Medicine, Tongji University, Shanghai, 200092, PR China.
FAU - Zhu, Zhounan
AU  - Zhu Z
AD  - Department of Oncology, East Hospital Affiliated to Tongji University, Tongji 
      University School of Medicine, Tongji University, Shanghai, 200092, PR China.
FAU - Jia, Xinyan
AU  - Jia X
AD  - Jinzhou Medical University, Jinzhou, Liaoning, 121000, PR China.
FAU - Ma, Yabin
AU  - Ma Y
AD  - Department of Pharmacy, East Hospital Affiliated to Tongji University, Tongji 
      University School of Medicine, Tongji University, Shanghai, 200092, PR China.
FAU - Dong, Chunyan
AU  - Dong C
AD  - Department of Oncology, East Hospital Affiliated to Tongji University, Tongji 
      University School of Medicine, Tongji University, Shanghai, 200092, PR China.
LA  - eng
PT  - Journal Article
DEP - 20240112
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC10835298
OTO - NOTNLM
OT  - ATF4
OT  - Biomarker
OT  - Breast cancer
OT  - MDA-MB-231
OT  - Treg
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/02/05 06:42
MHDA- 2024/02/05 06:43
PMCR- 2024/01/12
CRDT- 2024/02/05 04:21
PHST- 2023/11/08 00:00 [received]
PHST- 2024/01/03 00:00 [revised]
PHST- 2024/01/11 00:00 [accepted]
PHST- 2024/02/05 06:43 [medline]
PHST- 2024/02/05 06:42 [pubmed]
PHST- 2024/02/05 04:21 [entrez]
PHST- 2024/01/12 00:00 [pmc-release]
AID - S2405-8440(24)00700-X [pii]
AID - e24669 [pii]
AID - 10.1016/j.heliyon.2024.e24669 [doi]
PST - epublish
SO  - Heliyon. 2024 Jan 12;10(2):e24669. doi: 10.1016/j.heliyon.2024.e24669. 
      eCollection 2024 Jan 30.