BTK Has Potential to Be a Prognostic Factor for Lung Adenocarcinoma and an Indicator for Tumor Microenvironment Remodeling: A Study Based on TCGA Data Mining
BTK Has Potential to Be a Prognostic Factor for Lung Adenocarcinoma and an Indicator for Tumor Microenvironment Remodeling: A Study Based on TCGA Data Mining
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BTK有潜力成为肺腺癌的预后因素和肿瘤微环境重塑的指标：基于TCGA数据挖掘的研究
DOI：
10.3389/fonc.2020.00424
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发表时间：
2020-04-15
影响因子：
4.7
通讯作者：
Li, Bo
中科院分区：
文献类型：
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作者：
Bi, Ke-Wei;Wei, Xu-Ge;Li, Bo
肿瘤微环境（TME）在肺腺癌（LUAD）的发生和发展中起着至关重要的作用;然而，在了解TME中免疫和基质成分的动态调节方面仍然存在挑战。在本研究中，我们应用CIBERSORT和ESTIMATE计算方法计算肿瘤浸润免疫细胞（TIC）的比例和免疫和基质成分的量在551例LUAD从癌症基因组图谱（TCGA）数据库。通过考克斯回归分析和蛋白质相互作用（PPI）网络构建对差异表达基因（DEG）进行分析。通过单变量考克斯与PPI的交叉分析，确定布鲁顿酪氨酸激酶（BTK）为预测因子。进一步分析发现BTK表达与LUAD患者的临床病理特征（临床分期、远处转移）呈负相关，与生存率呈正相关。基因集富集分析（GSEA）显示，高表达BTK组中的基因主要富集在免疫相关活性方面。在低表达BTK组中，基因在代谢途径中富集。TIC比例的CIBERSORT分析显示，B细胞记忆和CD 8 + T细胞与BTK表达呈正相关，这表明BTK可能是TME免疫优势状态保持的原因。因此，BTK水平可能有助于概述LUAD患者的预后，特别是TME状态从免疫主导向代谢活性转变的线索，这为LUAD的治疗提供了额外的见解。
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.