Lung tumors frequently metastasize to the brain. Brain metastasis (BM) is common in advanced cases, and a major cause of patient morbidity and mortality. The precise molecular mechanisms governing BM are still unclear, in part attributed to the rarity of BM specimens. In this work, we compile a unique transcriptomic dataset encompassing RNA-seq, microarray, and single-cell analyses from BM samples obtained from patients with lung adenocarcinoma (LUAD). By integrating this comprehensive dataset, we aimed to enhance understanding of the molecular landscape of BM, thereby facilitating the identification of novel and efficient treatment strategies. We identified 102 genes with significantly deregulated expression levels in BM tissues, and discovered transcriptional alterations affecting the key driver ‘hub’ genesCD69(a type II C-lectin receptor) andGZMA(Granzyme A), indicating an important role of the immune system in the development of BM from primary LUAD. Our study demonstrated a BM-specific gene expression pattern and revealed the presence of dendritic cells and neutrophils in BM, suggesting an immunosuppressive tumor microenvironment. These findings highlight key drivers of LUAD-BM that may yield therapeutic targets to improve patient outcomes.
肺肿瘤常发生脑转移。脑转移在晚期病例中较为常见，是导致患者发病和死亡的主要原因。目前对脑转移的精确分子机制尚不明确，部分原因在于脑转移样本的稀缺性。本研究整合了来自肺腺癌患者脑转移样本的RNA测序、微阵列及单细胞分析数据，构建了一个独特的转录组学数据集。通过综合分析该数据集，我们旨在深化对脑转移分子特征的理解，从而促进新型高效治疗策略的发现。我们在脑转移组织中鉴定出102个表达水平显著失调的基因，并发现关键驱动枢纽基因CD69（一种II型C型凝集素受体）和GZMA（颗粒酶A）的转录水平发生改变，表明免疫系统在原发肺腺癌发展为脑转移的过程中发挥重要作用。研究揭示了脑转移特异性基因表达模式，并发现脑转移组织中存在树突状细胞和中性粒细胞，提示肿瘤微环境处于免疫抑制状态。这些发现明确了肺腺癌脑转移的关键驱动因素，可能为改善患者预后提供潜在治疗靶点。
肿瘤(癌症)患者之家