NDLI: Potential role of CFLAR in enhancing 5-FU sensitivity and modulating immune cell infiltration in breast cancer

Content Provider	Springer Nature : BioMed Central
Author	Sun, Yuwei Fang, Weilun Peng, Jinwu Liu, Xingling Wang, Chunjiang Song, Liying Deng, Zhenzhen
Abstract	Background Breast cancer (BRCA), the most common malignancy among women, is a highly heterogeneous disease. Chemoresistance is a major factor leading to treatment failure in BRCA. However, mechanisms underlying the development of chemoresistance remain unclear. Methods In this study, we performed a comprehensive bioinformatic analysis to examine the role of cell death-associated genes in BRCA treatment. Specifically, we focused on caspase 8 and Fas-associated protein with death domain-like apoptosis regulator (CFLAR), which was identified as a co-differentially expressed cell death-associated molecule with potential prognostic values. We then validated these findings through in vitro experiments in BT- 549 and MDA-MB- 231 breast cancer cells. Results Based on bioinformatics analysis, CFLAR expression was found to be downregulated in patients with BRCA, whereas its high expression was significantly associated with improved prognosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that aberrantly expressed CFLAR was potentially associated with oxidative phosphorylation, T cell receptor signaling, and NADH dehydrogenase (ubiquinone) activity. In vitro experiments demonstrated that overexpression of CFLAR inhibited the generation of reactive oxygen species (ROS), consequently promoting 5-fluorouracil (5-FU) sensitivity in BT- 549 and MDA-MB- 231 breast cancer cells. The expression of CFLAR was positively correlated with the abundance of several tumor-infiltrating immune cells, especially CD8 + T cells, further supporting the role of CFLAR in immune regulation. Conclusion In conclusion, this study reveals the novel roles of CFLAR in enhancing chemotherapy sensitivity and patient outcome in BRCA and underscores its potential as a therapeutic target. These results supported CFLAR as a therapeutic target and prognostic biomarker in BRCA patients.
Related Links	https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-025-02532-4.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s40001-025-02532-4
Journal	European Journal of Medical Research
Issue Number	1
Volume Number	30
Language	English
Publisher	BioMed Central
Publisher Date	2025-04-10
Access Restriction	Open
Subject Keyword	Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Breast cancer CFLAR ROS Immune infiltration 5-Fluorouracil Chemoresistance Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	2.9/2023

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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