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铁死亡相关基因 AKR1C1  作为与免疫微环境和乳腺癌预后相关的新型生物标志物的评价

 

Authors Zhang Z, Qiu X , Yan Y, Liang Q, Cai Y, Peng B, Xu Z , Xia F

Received 12 July 2021

Accepted for publication 24 August 2021

Published 28 September 2021 Volume 2021:14 Pages 6189—6200

DOI https://doi.org/10.2147/IJGM.S329031

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Scott Fraser

Background: Ferroptosis is the latest-discovered, iron-dependent form of regulated cell death. It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (BRCA ). Thus, It is important to explore the biofunctions of ferroptosis-related genes in BRCA .
Methods: Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA-BRCA  were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in BRCA .
Results: Two ferroptosis-related genes (AKR1C1  and AKR1C3 ) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of AKR1C1  was related with favorable prognosis. TCGA-BRCA  further confirmed the expression of AKR1C1  and the prognostic value of AKR1C1 . Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed AKR1C1  was significantly associated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, AKR1C1  was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of AKR1C1  in the immune reaction during the pathogenesis of breast cancer.
Conclusion: This study firstly demonstrated that ferroptosis-related gene, AKR1C1 , could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.
Keywords: breast cancer, AKR1C1, ferroptosis, immune microenvironment, immune infiltration