基于单细胞数据分析肺腺癌脑转移微环境中B细胞的作用

The role of B cells in the brain metastasis microenvironment of lung adenocarcinoma was analyzed by single-cell analysis

目的通过对肺腺癌的单细胞数据进行分析, 着眼于B细胞在肺腺癌发生和发展中的动态变化, 刻画B细胞在肺腺癌肿瘤微环境中的作用。方法对肺腺癌患者的单细胞数据进行分析, 使用NormalizeData和ScaleData函数对原始读取计数归一化, 消退基因表达的细胞间差异。使用"FindVariableFeatures"计算组间高表达基因。使用SingleR辅助进行细胞类别注释, 使用monocle2对10种B细胞亚类细胞进行拟时序分析, 差异表达基因进行GO通路富集分析。结果相对正常肺组织, B细胞在肺癌组织中分布相对较多, 其中记忆性B细胞和浆细胞显著增多;而在脑转移组织中, 浆细胞显著增多。对各组织的差异基因进行富集分析发现, 在肺癌原发灶中免疫B细胞对癌细胞产生强烈的免疫反应;而浆细胞在脑转移瘤中的作用主要是抑制细胞生长、保证细胞和组织的稳定, 一定程度上缓解肿瘤细胞入侵其他组织的伤害。结论基于单细胞分析可以进一步了解B细胞在肺腺癌发生和脑转移过程中的作用机制, 对肺腺癌脑转移的免疫临床应用提供理论基础。

Objective Focusing on the dynamic changes of B cells in the development and progression of lung adenocarcinoma,the role of B cells in the tumor microenvironment of lung adenocarcinoma was preliminarily elucidated by analyzing the single-cell data of lung adenocarcinoma.Methods Single-cell data of lung adenocarcinoma were analyzed,raw read counts were normalized using the NormalizeData function,and cell-to-cell differences in gene expression were eliminated using the ScaleData function.Use"FindVariableFeatures"to calculate high-expression genes between groups.After cell clustering,SingleR-assisted cell class annotation was performed,10 B-cell subclass cells were time-quasi-sequence analysis using monocle2,differences between genes in different states were calculated and heat maps were drawn,differentially expressed genes were enriched by GO pathway.Results B cells are rarely distributed in normal lung tissue,and relatively more in tumor tissue.Among them,the number of memory B cells and plasma cells in the lung primary lesion increased significantly,in brain metastases,plasma cells were significant,and the differential genes in various tissues were enriched and analyzed,and it was found that immune B cells in the primary tumor of lung cancer produced a strong immune response to cancer cells,and when the tumor cells metastasized,the role of plasma cells in brain metastases was mainly to inhibit cell growth,ensure the stability of cells and tissues,and alleviate the damage of tumor cells invading other tissues to a certain extent.Conclusion Based on single-cell analysis,the mechanism of action of B cells in the pathogenesis and brain metastasis of lung adenocarcinoma can be further understood,and the clinical application of immunity to lung adenocarcinoma brain metastasis can be further understood.