Multi-omics analysis identified serum <i>B4GALT1</i> as a prognostic factor for small cell lung cancer

<h4>Background</h4>Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid progression, early metastasis, and high mortality, with limited effective long-term treatment options. <i>B4GALT1</i>, a β-1,4-galactosyltransferase, has been implicated in the malignant progression of various cancers, but its specific role and underlying mechanisms in SCLC remain largely unexplored. We conducted a multi-omics analysis and clinical sample study to explore the function of <i>B4GALT1</i> in SCLC.<h4>Methods</h4>This study comprehensively investigated the expression pattern, functional significance, and clinical relevance of <i>B4GALT1</i> in SCLC. We conducted multi-omics analyses, including single-cell data processing, InferCNV analysis, and immune infiltration analysis, to explore the association between <i>B4GALT1</i> and the immune microenvironment of SCLC and patient survival. To determine <i>B4GALT1</i> as a potential circulating biomarker, quantitative data-independent acquisition (DIA) proteomics analysis was performed on serum samples from SCLC patients and healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to further verify the differential expression of serum <i>B4GALT1</i> in a larger cohort of SCLC patients, to evaluate its diagnostic, prognostic, and treatment response predictive value.<h4>Results</h4>Multi-omics analysis revealed that <i>B4GALT1</i> expression was significantly associated with patient survival. The expression of <i>B4GALT1</i> positively correlated with macrophage infiltration in the tumor and negatively correlated with CD4⁺ T cells in the tumor. There was a negative correlation in inactivated naïve B cells, eosinophils, and CD4 naïve T cells, while it showed a positive correlation in dendritic cells, M0/M1/M2 macrophages, natural killer (NK) cells, CD8 T cells, follicular helper T cells, and regulatory T cells. ELISA results showed that serum protein <i>B4GALT1</i> expression was higher in patients with SCLC than in healthy controls. Elevated serum B4GALT1 protein levels correlated with poor treatment outcomes in patients with SCLC undergoing chemoradiotherapy.<h4>Conclusions</h4>Our findings establish <i>B4GALT1</i> as a critical prognostic, diagnostic, and predictive biomarker in SCLC, with its expression closely linked to the tumor immune microenvironment and treatment response. Targeting <i>B4GALT1</i> or its related pathways may represent a novel therapeutic strategy, and serum <i>B4GALT1</i> holds promise as a liquid biopsy marker for SCLC patient stratification, monitoring, and guiding treatment decisions.