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L-Selectin expression is associated with inflammatory microenvironment and favourable prognosis in breast cancer
3 Biotech ( IF 2.8 ) Pub Date : 2021-01-08 , DOI: 10.1007/s13205-020-02549-y
Sarita Kumari 1 , Mohit Arora 2 , Jay Singh 1 , Shyam S Chauhan 2 , Sachin Kumar 3 , Anita Chopra 1
Affiliation  

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.



中文翻译:

L-选择素表达与炎症微环境和乳腺癌的良好预后相关

L-选择素是一种细胞粘附分子,在调节免疫细胞运输中起重要作用。已发现 L-选择素的表达在几种人类癌症中上调。然而,尚未详细探讨 L-选择素表达与免疫谱及其在乳腺癌中的预后价值的关联。我们利用 TCGA 和 Oncomine 数据集来比较肿瘤和正常乳腺组织之间的SELL(L-选择素基因)表达。通过使用 Wanderer、TIMER 和 CIBERSORT 工具评估SELL表达与其启动子 DNA 甲基化和浸润免疫细胞的关联。单细胞 RNA 测序数据用于确定 L-选择素在乳腺癌中的细胞特异性表达。此外,之间的关系使用 Kaplan-Meier 绘图仪评估SELL表达和患者存活率。进行基因集富集分析以确定SELL表达的功能关联。我们发现SELL表达在乳腺肿瘤中显着升高,并受 DNA 甲基化的调节。L-选择素与包括 M1 巨噬细胞在内的炎症微环境标志物呈强正相关。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SELL表达水平,这表明 B 细胞和 T 细胞都有助于乳腺癌中的SELL表达。SELL的高表达与乳腺癌基底、Her2 + 和管腔 B 亚型更好的生存结果相关。GSEA 揭示了SELL表达与乳腺癌中几种免疫学特征的关联。SELL表达在乳腺肿瘤组织中增加,DNA 甲基化减少和相关的炎症微环境。此外,高SELL表达与乳腺癌的良好生存结果相关。

更新日期:2021-01-08
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