Association of SMOX gene expression with immune checkpoint therapy response in patients with non-small cell lung cancer.

Abstract

e14559 Background: SMOX is a gene encoding spermine oxidase which is an important enzyme in the catabolism of polyamines. It is associated with tumor progression and prognosis. High expression of SMOX is correlated with poor prognosis in non-small cell lung cancer patients. Here, we investigate the prognostic value of SMOX gene expression in patients with NSCLC and explore the potential mechanism. Methods: A bioinformatics analysis was conducted to identify differentially expressed genes (DEGs) related to NSCLC prognosis, using datasets from the gene expression omnibus (GEO) and the cancer genome atlas (TCGA). Gene set enrichment analysis (GSEA) and TIMER 2.0 were applied to explore the correlation between SMOX expression and immune cell infiltration. Single-cell analysis elucidated SMOX expression patterns in immune subpopulations. Results: There were 227 genes related to the prognosis of NSCLC screened from 1,043 non-small cell lung cancer samples and 110 normal tissue samples. Twenty-nine genes associated with the efficacy of immunotherapy in NSCLC were identified through differential gene analysis of the GSE111414 dataset. SMOX was a member of both sets and was considered a gene of interest. Survival curves indicated that patients with low SMOX expression had better prognosis (p < 0.05). The FcεRI pathway was regulated down when SMOX expression was low and was regulated up when SMOX expression was high (FDR q-value = 0.20, p = 0.006). The infiltration levels of T cells(p < 0.01) and NK cells(p = 0.021) were higher in the low expression group. Conversely, the infiltration levels of mast cells(p < 0.001), macrophages(p < 0.001) and dendritic cells(p = 0.015) were higher in the high expression group. There were 8 immune cell subpopulations after single-cell analysis which were epithelial cells, T cells, monocytes, macrophages, B cells, tissue stem cells, endothelial cells, and NK cells. SMOX was expressed higher in monocytes and macrophages compared to other cell types. The macrophages in which SMOX was expressed higher highly expressed genes (SCGB1A1, LYN, PTPRE and MIR155HG) associated with mast cell degranulation and tumor proliferation. Conclusions: Theses findings suggest that SMOX can affect tumor microenvironment and may regulate the activation state of mast cells by affecting the FcεRI signaling pathway. It could serve as a biomarker for immunotherapy response and a potential therapeutic target for non-small cell lung cancer.