Kumari Sarita, Arora Mohit, Singh Jay, Chauhan Shyam S, Kumar Sachin, Chopra Anita
Laboratory Oncology Unit, Dr. BRA-IRCH, All India Institute of Medical Sciences, New Delhi, India.
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
3 Biotech. 2021 Feb;11(2):38. doi: 10.1007/s13205-020-02549-y. Epub 2021 Jan 8.
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 (L-selectin gene) expression between tumor and normal breast tissues. The association of 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 expression and patient survival was evaluated using the Kaplan-Meier plotter. Gene set enrichment analysis was performed to determine functional associations of expression. We found that 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 , suggesting both B-cells and T cells contribute to expression in breast cancer. Higher expression of was associated with better survival outcome in basal, Her2 + and luminal B subtypes of breast cancer. GSEA revealed association of expression with several immunological features in breast cancer. expression increases in breast tumor tissues with reduced DNA methylation and associated inflammatory microenvironment. Also, high expression is associated with favorable survival outcomes in breast cancer.
L-选择素是一种细胞粘附分子，在调节免疫细胞运输中发挥重要作用。已发现L-选择素在几种人类癌症中表达上调。然而，L-选择素表达与免疫谱的关联及其在乳腺癌中的预后价值尚未得到详细研究。我们利用TCGA和Oncomine数据集比较肿瘤和正常乳腺组织之间的（L-选择素基因）表达。使用Wanderer、TIMER和CIBERSORT工具评估其表达与其启动子DNA甲基化和浸润免疫细胞的关联。利用单细胞RNA测序数据确定L-选择素在乳腺癌中的细胞特异性表达。此外，使用Kaplan-Meier绘图仪评估表达与患者生存之间的关系。进行基因集富集分析以确定表达的功能关联。我们发现乳腺癌中L-选择素的表达显著更高且受DNA甲基化调节。L-选择素与炎症微环境标志物（包括M1巨噬细胞）呈强正相关。有趣的是，单细胞测序数据分析显示B细胞和T细胞表现出相当的L-选择素表达水平，表明B细胞和T细胞均对乳腺癌中L-选择素的表达有贡献。L-选择素的高表达与乳腺癌基底型、Her2+和管腔B亚型更好的生存结果相关。基因集富集分析揭示了L-选择素表达与乳腺癌的几种免疫特征的关联。随着DNA甲基化减少和相关炎症微环境，乳腺癌组织中L-选择素表达增加。此外，L-选择素的高表达与乳腺癌良好的生存结果相关。
