Abstract
L-selectin is a cell adhesion molecule that plays an important role in modulating immune cell trafficking. The expression of L-selectin has been found to be upregulated in several human cancers. However, the association of L-selectin expression with the immune profile and its prognostic value in breast cancer has not been explored in detail. We utilized TCGA and Oncomine datasets to compare SELL (L-selectin gene) expression between tumor and normal breast tissues. The association of SELL expression with its promoter DNA methylation and infiltrating immune cells was evaluated by using Wanderer, TIMER, and CIBERSORT tools. Single cell RNA sequencing data was utilised to determine the cell specific expression of L-selectin in breast cancer. Furthermore, the relationship between SELL expression and patient survival was evaluated using the Kaplan–Meier plotter. Gene set enrichment analysis was performed to determine functional associations of SELL expression. We found that SELL expression was significantly higher in breast tumors and regulated by DNA methylation. L-selectin exhibited a strong positive correlation with markers of the inflammatory microenvironment, including M1 macrophages. Interestingly, single cell sequencing data analysis revealed that B-cells and T-cells exhibited comparable expression levels of SELL, suggesting both B-cells and T cells contribute to SELL expression in breast cancer. Higher expression of SELL was associated with better survival outcome in basal, Her2 + and luminal B subtypes of breast cancer. GSEA revealed association of SELL expression with several immunological features in breast cancer. SELL expression increases in breast tumor tissues with reduced DNA methylation and associated inflammatory microenvironment. Also, high SELL expression is associated with favorable survival outcomes in breast cancer.
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Acknowledgements
Anita Chopra acknowledges support from the Wellcome Trust/DBT India Alliance Fellowship (grant number: IA/CPHI/17/1/503333). Sarita Kumari acknowledges financial support as fellowship from Department of Health Research, Government of India. Jay Singh acknowledges financial support as fellowship from Department of Biotechnology, Government of India. Mohit Arora acknowledges financial support as fellowship from Council of Scientific and Industrial Research, Government of India.
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SK conceptualized the study and wrote the original manuscript. MA, SK, JS, and AC performed data analysis and interpretation. SSC, AC, and SK supervised the study and edited the manuscript.
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The current study was performed using publicly available datasets, which have been cited in the manuscript. The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.
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Kumari, S., Arora, M., Singh, J. et al. L-Selectin expression is associated with inflammatory microenvironment and favourable prognosis in breast cancer. 3 Biotech 11, 38 (2021). https://doi.org/10.1007/s13205-020-02549-y
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DOI: https://doi.org/10.1007/s13205-020-02549-y