Published online 2020 Apr 15. doi: 10.3389/fonc.2020.00424
Abstract
Tumor microenvironment (TME) plays a crucial role in the initiation and progression of lung adenocarcinoma (LUAD); however, there is still a challenge in understanding the dynamic modulation of the immune and stromal components in TME. In the presented study, we applied CIBERSORT and ESTIMATE computational methods to calculate the proportion of tumor-infiltrating immune cell (TIC) and the amount of immune and stromal components in 551 LUAD cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein-protein interaction (PPI) network construction. Then, Bruton tyrosine kinase (BTK) was determined as a predictive factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that BTK expression was negatively correlated with the clinical pathologic characteristics (clinical stage, distant metastasis) and positively correlated with the survival of LUAD patients. Gene Set Enrichment Analysis (GSEA) showed that the genes in the high-expression BTK group were mainly enriched in immune-related activities. In the low-expression BTK group, the genes were enriched in metabolic pathways. CIBERSORT analysis for the proportion of TICs revealed that B-cell memory and CD8+ T cells were positively correlated with BTK expression, suggesting that BTK might be responsible for the preservation of immune-dominant status for TME. Thus, the levels of BTK might be useful for outlining the prognosis of LUAD patients and especially be a clue that the status of TME transition from immune-dominant to metabolic activity, which offered an extra insight for therapeutics of LUAD.
Keywords: BTK; CIBERSORT; ESTIMATE; lung adenocarcinoma; tumor microenvironment; tumor-infiltrating immune cells.
BTK有可能成为肺腺癌的预后因素和肿瘤微环境重塑的指标:一项基于TCGA数据挖掘的研究
在这一部分,作者根据BTK中值表达将所有LUAD样本分为BTK高表达组和BTK低表达组。生存分析表明,高表达BTK的LUAD患者比低表达BTK的患者具有更长的生存期(图6C)。接下来作者进行了结合临床特征的BTK分析,Wilcoxon秩和检验表明,肿瘤样本中BTK的表达明显低于正常样本中的表达(图6A)。并且在同一患者的正常组织与肿瘤组织之间的配对分析中观察到了相似的结果(图6B)。这些结果表明,TME中BTK的表达与LUAD患者的预后呈正相关。尤其是,随着TNM分期的进展,BTK的表达下降(图6D-G)。
图6. BTK在样本中的差异表达及其与LUAD患者的生存和临床病理分期特征的关系
转自生信人