Transcription Factors Leading to High Expression of Neuropeptide L1CAM in Brain Metastases from Lung Adenocarcinoma and Clinical Prognostic Analysis

BACKGROUND: 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. METHODS: 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. RESULTS: Survival analysis suggested that high L1CAM expression was negatively significantly associated with overall survival, disease-specific survival, and prognosis in the progression-free interval (p < 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. CONCLUSION: 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.