AUTHOR=Jiang Tongchao , Wang Ying , Chen Xiaoyu , Xia Wen , Xue Shuyu , Gu Liwen , Guo Ling , Lin Huanxin 

TITLE=Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1117637

DOI=10.3389/fcell.2023.1117637

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> Neutrophil extracellular traps (NETs) are closely associated to tumorigenesis and development. However, the relationship between NETs-related long non-coding RNAs (lncRNAs) and the characteristics of breast tumor remains an enigma. This study aimed to explore the clinical prognostic value of NETs-related lncRNAs, their correlation with the tumor microenvironment (TME) and their predictive ability of drug sensitivity in patients with breast cancer (BC).</p><p><bold>Methods:</bold> The expression profiles of RNA-sequencing and relevant clinical data of BC patients were extracted from TCGA database. The co-expression network analysis, univariable, least absolute shrinkage and selection operator (LASSO) and multivariable Cox algorithms were employed to construct the NETs-related lncRNAs signature. A nomogram was established and validated to explore the clinical application. Furthermore, the immune microenvironment and drug sensitivity for BC with different prognostic risks were explored. Finally, the expression pattern of lncRNAs was validated using qRT-PCR in BC tissues and their adjacent non-cancerous tissues.</p><p><bold>Results:</bold> Based on NETs-related lncRNAs, a prognostic risk model consisted of 10 lncRNAs (SFTA1P, ACTA2-AS1, AC004816.2, AC000067.1, LINC01235, LINC01010, AL133467.1, AC092919.1, AL591468.1, and MIR200CHG) was established. The Kaplan-Meier analysis showed that the overall survival (OS) was significantly better in low-risk BC patients than in high-risk BC patients (<italic>P</italic><sub>training cohort</sub> &lt; 0.001, <italic>P</italic><sub>validation cohort</sub> = 0.009). The nomogram also showed good predictive accuracy for OS of BC individuals in both training and validation cohorts. The function enrichment analysis revealed that high-risk group was mainly enriched in immune-related functions and pathways, and the tumor mutation burden in this group was markedly higher than that in the low-risk group (<italic>p</italic> = 0.022). Moreover, significant differences were observed in immune cells, immune functions and immune checkpoint genes among BC patients at different risks (<italic>p</italic> &lt; 0.05). The response to chemotherapeutic agents and immunotherapy were also closely related with the expression of NETs-related lncRNAs (<italic>p</italic> &lt; 0.001). The expression of lncRNAs from experimental validation were generally consistent with the bioinformatics analysis results.</p><p><bold>Conclusion:</bold> Our study provided a novel prognostic model for BC and yielded strong scientific rationale for individualized treatment strategies, elucidating immunotherapy in BC patients.</p>