Low expression of NR1H3 correlates with macrophage infiltration and indicates worse survival in breast cancer

NR1H3 表达降低与巨噬细胞浸润相关,提示乳腺癌生存率较低

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作者:Jing Zhang, Jiawen Zhang, Weiwei Zhao, Qingxian Li, Wenwu Cheng

Background

Nuclear receptor NR1H3 is a key regulator of macrophage function and lipid homeostasis. Here, we aimed to visualize the prognostic value and immunological characterization of NR1H3 in breast cancer.

Conclusion

These findings suggest that NR1H3 serves as a prognostic biomarker and contributes to the regulation of macrophage activation in breast cancer.

Methods

The expression pattern and prognostic value of NR1H3 were analyzed via multiple databases, including TIMER2, GEPIA2 and Kaplan-Meier Plotter. TISIDB, TIMER2 and immunohistochemical analysis were used to investigate the correlation between NR1H3 expression and immune infiltration. GO enrichment analysis, KEGG analysis, Reactome analysis, ConsensusPathDB and GeneMANIA were used to visualize the functional enrichment of NR1H3 and signaling pathways related to NR1H3.

Results

We demonstrated that the expression of NR1H3 was significantly lower in breast cancer compared with adjacent normal tissues. Kaplan-Meier survival curves showed shorter overall survival in basal breast cancer patients with low NR1H3 expression, and poorer prognosis of relapse-free survival in breast cancer patients with low NR1H3 expression. NR1H3 was mainly expressed in immune cells, and its expression was closely related with infiltrating levels of tumor-infiltrating immune cells in breast cancer. Additionally, univariate and multivariate analysis indicated that the expression of NR1H3 and the level of macrophage infiltration were independent prognostic factors for breast cancer. Gene interaction network analysis showed the function of NR1H3 involved in regulating of innate immune response and macrophage activation. Moreover, NR1H3 may function as a predictor of chemoresponsiveness in breast cancer.

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