Department of Neurosurgery, The First Affiliated Hospital of Jinzhou Medical University, China.
Department of Neurointervention, The First Affiliated Hospital of Jinzhou Medical University, China.
Dis Markers. 2021 Dec 30;2021:8585633. doi: 10.1155/2021/8585633. eCollection 2021.
There is a lack of understanding of the development of metastasis in lung adenocarcinoma (LUAD). This study is aimed at exploring the upstream regulatory transcription factors of L1 cell adhesion molecule (L1CAM) and to construct a prognostic model to predict the risk of brain metastasis in LUAD.
Differences in gene expression between LUAD and brain metastatic LUAD were analyzed using the Wilcoxon rank-sum test. The GRNdb (http://www.grndb.com) was used to reveal the upstream regulatory transcription factors of L1CAM in LUAD. Single-cell expression profile data (GSE131907) were obtained from the transcriptome data of 10 metastatic brain tissue samples. LUAD prognostic nomogram prediction models were constructed based on the identified significant transcription factors and L1CAM.
Survival analysis suggested that high L1CAM expression was negatively significantly associated with overall survival, disease-specific survival, and prognosis in the progression-free interval ( < 0.05). The box plot indicates that high expression of L1CAM was associated with distant metastases in LUAD, while ROC curves suggested that high expression of L1CAM was associated with poor prognosis. FOSL2, HOXA9, IRF4, IKZF1, STAT1, FLI1, ETS1, E2F7, and ADARB1 are potential upstream transcriptional regulators of L1CAM. Single-cell data analysis revealed that the expression of L1CAM was found significantly and positively correlated with the expression of ETS1, FOSL2, and STAT1 in brain metastases. L1CAM, ETS1, FOSL2, and STAT1 were used to construct the LUAD prognostic nomogram prediction model, and the ROC curves suggest that the constructed nomogram possesses good predictive power.
By bioinformatics methods, ETS1, FOSL2, and STAT1 were identified as potential transcriptional regulators of L1CAM in this study. This will help to facilitate the early identification of patients at high risk of metastasis.
目前人们对肺腺癌（LUAD）转移的发展过程了解甚少。本研究旨在探讨 L1 细胞黏附分子（L1CAM）的上游调控转录因子，并构建预测 LUAD 脑转移风险的预后模型。
采用 Wilcoxon 秩和检验分析 LUAD 和脑转移 LUAD 之间的基因表达差异。使用 GRNdb（http://www.grndb.com）揭示 LUAD 中 L1CAM 的上游调控转录因子。从 10 个转移性脑组织样本的转录组数据中获取单细胞表达谱数据（GSE131907）。基于鉴定的显著转录因子和 L1CAM 构建 LUAD 预后诺莫图预测模型。
生存分析表明，L1CAM 高表达与 LUAD 的总生存期、疾病特异性生存期和无进展生存期预后不良显著相关（<0.05）。箱线图表明，L1CAM 高表达与 LUAD 的远处转移相关，而 ROC 曲线表明，L1CAM 高表达与预后不良相关。FOSL2、HOXA9、IRF4、IKZF1、STAT1、FLI1、ETS1、E2F7 和 ADARB1 是 L1CAM 的潜在上游转录调控因子。单细胞数据分析显示，L1CAM 的表达与脑转移中 ETS1、FOSL2 和 STAT1 的表达呈显著正相关。使用 L1CAM、ETS1、FOSL2 和 STAT1 构建 LUAD 预后诺莫图预测模型，ROC 曲线表明构建的诺莫图具有良好的预测能力。
本研究通过生物信息学方法鉴定出 ETS1、FOSL2 和 STAT1 是 L1CAM 的潜在转录调控因子，有助于早期识别高转移风险的患者。
