IntroductionLung adenocarcinoma (LUAD) is the major type of non-small cell lung cancer with low a survival rate caused by metastasis. SCN4B encoding voltage-gated sodium channel beta subunit is regarded as a metastasis-suppressor gene. We aim to explore how SCN4B influences the progression and prognosis of LUAD.MethodsThe gene expression profiles of 585 LUAD samples in TCGA and GSE31210, GSE116959, and GSE72094 datasets from the GEO database were downloaded for analysis. Differentially expressed genes were obtained through the "limma" package. The "clusterProfiler" package was used to conduct GSEA. Survival analysis was conducted via "survival" and "survminer" packages. Transcription factors regulating SCN4B expression were screened by correlation analysis and further predicted by FIMO. Infiltration of immune cells was analyzed by CIBERSORT. ESTIMATE algorithm was used to evaluate the immune-related scores.ResultsSCN4B expressed higher in normal samples than in LUAD samples and higher in female samples than male samples. One hundred and twenty-six pathways were significantly enriched between high and low SCN4B expression groups. Six transcription factors' expressions were positively related to SCN4B expression, and ChIP-seq data from "Cistrome" verified that TAL1 and ERG might bind to the upstream sequence of SCN4B. SCN4B expression was significantly correlated with activated memory CD4 T cells, resting mast cells, and monocytes. TMB status, three scores based on ESTIMATE algorithm, and expression of three immune checkpoints showed significant differences between SCN4B high- and low-expression groups. SCN4B could be considered as an independent prognostic signature of LUAD patients that higher expression represents a better prognosis.ConclusionSCN4B expresses higher in normal samples, and SCN4B is able to be an independent prognostic signature for LUAD patients. TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences. Our research is valuable in improving the effectiveness of treatment in LUAD. SCN4B encoding voltage-gated sodium channel beta subunit is regarded as metastasis-suppressor gene, and it expresses higher in normal samples than lung adenocarcinoma (LUAD) samples. SCN4B is an independent prognostic signature for LUAD patients, and its higher expression in LUAD samples represents better prognosis. Transcription factors TAL1 and ERG may regulate the expression of SCN4B by binding its upstream sequences.image